Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_030621.4(DICER1):c.*5G>A

CA7330592

315099 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 55ffbbe6-abce-4a5d-921f-a9db595fb431
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_030621.4:c.*5G>A
NM_030621.4(DICER1):c.*5G>A
NC_000014.9:g.95090493C>T
CM000676.2:g.95090493C>T
NC_000014.8:g.95556830C>T
CM000676.1:g.95556830C>T
NC_000014.7:g.94626583C>T
NG_016311.1:g.71930G>A
ENST00000343455.8:c.*5G>A
ENST00000393063.6:c.*5G>A
ENST00000526495.6:c.*5G>A
ENST00000675540.1:n.3519G>A
ENST00000675995.1:c.*4090G>A
ENST00000343455.7:c.*5G>A
ENST00000393063.5:c.*5G>A
ENST00000526495.5:c.*5G>A
ENST00000527414.5:c.*5G>A
ENST00000527416.2:n.347+20G>A
ENST00000541352.5:c.*121G>A
ENST00000556045.5:c.*5G>A
NM_001195573.1:c.*121G>A
NM_001271282.2:c.*5G>A
NM_001291628.1:c.*5G>A
NM_177438.2:c.*5G>A
NM_001271282.3:c.*5G>A
NM_001291628.2:c.*5G>A
NM_177438.3:c.*5G>A
NM_001395677.1:c.*5G>A
NM_001395678.1:c.*5G>A
NM_001395679.1:c.*5G>A
NM_001395680.1:c.*5G>A
NM_001395682.1:c.*5G>A
NM_001395683.1:c.*5G>A
NM_001395684.1:c.*5G>A
NM_001395685.1:c.*320G>A
NM_001395686.1:c.*5G>A
NM_001395687.1:c.*5G>A
NM_001395688.1:c.*5G>A
NM_001395689.1:c.*5G>A
NM_001395690.1:c.*5G>A
NM_001395691.1:c.*5G>A
NM_001395697.1:c.*5G>A
NR_172715.1:n.6172+20G>A
NR_172716.1:n.6376G>A
NR_172717.1:n.6266+20G>A
NR_172718.1:n.6209G>A
NR_172719.1:n.6042G>A
NR_172720.1:n.6245G>A
NM_177438.3(DICER1):c.*5G>A
More

Likely Benign

Met criteria codes 2
BP4 BS2_Supporting
Not Met criteria codes 13
BS1 BS3 BP7 PVS1 BA1 PS1 PS3 PS4 PP3 PP4 PM2 PM1 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen DICER1 and miRNA-Processing Gene Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DICER1 Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
The NM_177438.2:c.*5G>A variant in DICER1 is an variant located five nucleotides into the 3' untranslated region (UTR) of the DICER1 gene. This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; SCV000661852.3). The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000085 (2/2350 alleles) in African/African-American population. (PM2_Supporting, BS1, and BA1 are not met). The splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as LIKELY BENIGN for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, BP4. (VBayesian Points: -2; VCEP specifications version 1; 02/11/2022)
Met criteria codes
BP4
The splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4).
BS2_Supporting
This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; SCV000661852.3). 35 females tumor free through age 50 at Ambry
Not Met criteria codes
BS1
The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000085 (2/2350 alleles) in African/African-American population. (PM2_Supporting, BS1, and BA1 are not met)
BS3
No studies found.
BP7
This variant does not show splicing impact (MaxEntScan and SpliceAI), but the nucleotide appears to be highly conserved. Although G>C is the reference nucleotide for multiple primates and other mammals, the only mammal with G>A as the reference nucleotide is the squirrel.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000085 (2/2350 alleles) in African/African-American population. (PM2_Supporting, BS1, and BA1 are not met)
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No studies found.
PS4
This variant has been observed in approx. 70 internal cases. It was also seen once in a 3 month old with CCAM who also carried a DICER1 frameshift variant.
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000085 (2/2350 alleles) in African/African-American population. (PM2_Supporting, BS1, and BA1 are not met)
PM1
This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.