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 obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!


Variant: NM_177438.3(DICER1):c.1140G>C (p.Leu380=)

CA7331523

483434 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: 8dff269f-4d8d-47d4-af57-d681c096bdca
Approved on: 2024-06-25
Published on: 2024-07-30

HGVS expressions

NM_177438.3:c.1140G>C
NM_177438.3(DICER1):c.1140G>C (p.Leu380=)
NC_000014.9:g.95124432C>G
CM000676.2:g.95124432C>G
NC_000014.8:g.95590769C>G
CM000676.1:g.95590769C>G
NC_000014.7:g.94660522C>G
NG_016311.1:g.37991G>C
ENST00000529720.2:c.1140G>C
ENST00000531162.7:c.1140G>C
ENST00000674628.2:c.1140G>C
ENST00000675540.2:c.1140G>C
ENST00000696733.1:c.1140G>C
ENST00000696734.1:c.1140G>C
ENST00000696736.1:c.1140G>C
ENST00000696737.1:c.1140G>C
ENST00000696921.1:n.2246G>C
ENST00000696922.1:n.1549G>C
ENST00000696923.1:c.1140G>C
ENST00000696924.1:c.1140G>C
ENST00000696925.1:n.1549G>C
ENST00000696927.1:n.743G>C
ENST00000696928.1:n.1337G>C
ENST00000343455.8:c.1140G>C
ENST00000393063.6:c.1140G>C
ENST00000526495.6:c.1140G>C
ENST00000532939.3:c.1140G>C
ENST00000556045.6:c.1140G>C
ENST00000674628.1:c.1140G>C
ENST00000675995.1:c.1140G>C
ENST00000343455.7:c.1140G>C
ENST00000393063.5:c.1140G>C
ENST00000526495.5:c.1140G>C
ENST00000527414.5:c.1140G>C
ENST00000541352.5:c.1140G>C
NM_001195573.1:c.1140G>C
NM_001271282.2:c.1140G>C
NM_001291628.1:c.1140G>C
NM_030621.4:c.1140G>C
NM_177438.2:c.1140G>C
NM_001271282.3:c.1140G>C
NM_001291628.2:c.1140G>C
NM_001395677.1:c.1140G>C
NM_001395678.1:c.1140G>C
NM_001395679.1:c.1140G>C
NM_001395680.1:c.1140G>C
NM_001395682.1:c.1140G>C
NM_001395683.1:c.1140G>C
NM_001395684.1:c.1140G>C
NM_001395685.1:c.1140G>C
NM_001395686.1:c.858G>C
NM_001395687.1:c.735G>C
NM_001395688.1:c.735G>C
NM_001395689.1:c.735G>C
NM_001395690.1:c.735G>C
NM_001395691.1:c.573G>C
NM_001395692.1:c.1140G>C
NM_001395693.1:c.1140G>C
NM_001395694.1:c.1140G>C
NM_001395695.1:c.1140G>C
NM_001395696.1:c.735G>C
NM_001395697.1:c.-429G>C
NM_001395698.1:c.735G>C
NM_001395699.1:c.1140G>C
NM_001395700.1:c.1140G>C
NR_172715.1:n.1354G>C
NR_172716.1:n.1485G>C
NR_172717.1:n.1652G>C
NR_172718.1:n.1652G>C
NR_172719.1:n.1485G>C
NR_172720.1:n.1485G>C
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 14
BP2 PS2 PS4 PS3 PP4 PP1 PP3 PM1 PM2 BA1 BS2 BS4 BS3 BS1

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.1140G>C (p.Leu380=) variant is a synonymous (silent) variant that is not predicted to impact splicing by MaxEntScan or SpliceAI (BP4, BP7). The total allele frequency in gnomAD v4.1.0 is 0.000006195 (10/1614118alleles) with a highest population minor allele frequency of 0.00008783 (8/91086alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are 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: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1.3.0; 06/28/2024)
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).
BP7
The NM_177438.2:c.1140G>C (p.Leu380=) variant is a synonymous (silent) variant that is not predicted to impact splicing by MaxEntScan or SpliceAI (BP4, BP7).
Not Met criteria codes
BP2
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
8 observations across 2 labs; no DICER1-specific phenotypes reported
PS3
None found.
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
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).
PM2
The total allele frequency in gnomAD v4.1.0 is 0.000006195 (10/1614118alleles) with a highest population minor allele frequency of 0.00008783 (8/91086alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
BA1
The total allele frequency in gnomAD v4.1.0 is 0.000006195 (10/1614118alleles) with a highest population minor allele frequency of 0.00008783 (8/91086alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
BS2
This variant has been seen in fewer than 10 unrelated females without tumors through age 50 in at least one testing laboratory (BS2 not met; Internal lab contributors). Invitae: 2 Ambry: 2
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
None found.
BS1
The total allele frequency in gnomAD v4.1.0 is 0.000006195 (10/1614118alleles) with a highest population minor allele frequency of 0.00008783 (8/91086alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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