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]
  • Gene label mismatch: DICER1 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.5623G>A (p.Asp1875Asn)

CA7330611

412160 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d7c1ed7f-5574-4f05-87f0-4b609c62c81d
Approved on: 2025-02-25
Published on: 2025-06-04

HGVS expressions

NM_177438.3:c.5623G>A
NM_177438.3(DICER1):c.5623G>A (p.Asp1875Asn)
NC_000014.9:g.95090644C>T
CM000676.2:g.95090644C>T
NC_000014.8:g.95556981C>T
CM000676.1:g.95556981C>T
NC_000014.7:g.94626734C>T
NG_016311.1:g.71779G>A
ENST00000529720.2:c.5623G>A
ENST00000531162.7:c.5623G>A
ENST00000674628.2:c.5623G>A
ENST00000675540.2:c.*2273G>A
ENST00000696733.1:c.*245G>A
ENST00000696734.1:c.*278G>A
ENST00000696735.1:n.2610G>A
ENST00000696736.1:c.*386G>A
ENST00000696920.1:n.5886G>A
ENST00000696921.1:n.6729G>A
ENST00000696922.1:n.8554G>A
ENST00000696923.1:c.*278G>A
ENST00000696924.1:c.*245G>A
ENST00000696925.1:n.8924G>A
ENST00000343455.8:c.5623G>A
ENST00000393063.6:c.5623G>A
ENST00000526495.6:c.5623G>A
ENST00000556045.6:c.*340G>A
ENST00000675540.1:c.3368G>A
ENST00000675995.1:c.*3939G>A
ENST00000343455.7:c.5623G>A
ENST00000393063.5:c.5623G>A
ENST00000526495.5:c.5623G>A
ENST00000527414.5:c.5623G>A
ENST00000527416.2:n.216G>A
ENST00000541352.5:c.5460G>A
ENST00000556045.5:c.2317G>A
NM_001195573.1:c.5460G>A
NM_001271282.2:c.5623G>A
NM_001291628.1:c.5623G>A
NM_030621.4:c.5623G>A
NM_177438.2:c.5623G>A
NM_001271282.3:c.5623G>A
NM_001291628.2:c.5623G>A
NM_001395677.1:c.5623G>A
NM_001395678.1:c.5623G>A
NM_001395679.1:c.5623G>A
NM_001395680.1:c.5623G>A
NM_001395682.1:c.5623G>A
NM_001395683.1:c.5623G>A
NM_001395684.1:c.5623G>A
NM_001395685.1:c.*169G>A
NM_001395686.1:c.5341G>A
NM_001395687.1:c.5218G>A
NM_001395688.1:c.5218G>A
NM_001395689.1:c.5218G>A
NM_001395690.1:c.5218G>A
NM_001395691.1:c.5056G>A
NM_001395697.1:c.3940G>A
NR_172715.1:n.6041G>A
NR_172716.1:n.6225G>A
NR_172717.1:n.6135G>A
NR_172718.1:n.6058G>A
NR_172719.1:n.5891G>A
NR_172720.1:n.6094G>A
More

Likely Benign

Met criteria codes 2
BP4 BS2_Supporting
Not Met criteria codes 16
BP2 BS4 BS3 BS1 PP4 PP1 PP3 PS2 PS4 PS3 PS1 BA1 PM6 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 1.3.0

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.5623G>A variant in DICER1 is a missense variant predicted to cause substitution of asparagine by aspartic acid at amino acid 1875 (p.Asp1875Asn). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00007811 (5/64012 alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.321, which is below the threshold of 0.5, and 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). Another missense variant c.5623G>T, p.Asp1875Tyr in the same codon has been reported (ClinVar Variation ID: 412042). However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met). In summary, this variant meets the criteria to be classified as likely benign for DICER1 related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, BP4 (Bayesian Points: -2; VCEP specifications version 1.3.0; 02/25/2025)
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.321, which is below the threshold of 0.5, and 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
Two internal clinical labs met BS2_supporting.
Not Met criteria codes
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No functional studies found
BS1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00007811 (5/64012 alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No phenotype points scored
PS3
No functional studies found
PS1
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 v4.1.0 is 0.00007811 (5/64012 alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PM6
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 v4.1.0 is 0.00007811 (5/64012 alleles) in European (Finnish) 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 (PM1 not met).
PM5
Another missense variant c.5623G>T, p.Asp1875Tyr in the same codon has been reported in a patient with DICER1 syndrome (ClinVar Variation ID: 412042). However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met).
Curation History
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