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 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_001005361.3(DNM2):c.643G>A (p.Asp215Asn)

CA9200848

416987 (ClinVar)

Gene: DNM2
Condition: centronuclear myopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 387c12dd-2a81-4f07-b830-414178ed3ec0
Approved on: 2024-08-07
Published on: 2024-10-01

HGVS expressions

NM_001005361.3:c.643G>A
NM_001005361.3(DNM2):c.643G>A (p.Asp215Asn)
NC_000019.10:g.10777171G>A
CM000681.2:g.10777171G>A
NC_000019.9:g.10887847G>A
CM000681.1:g.10887847G>A
NC_000019.8:g.10748847G>A
NG_008792.1:g.64093G>A
ENST00000682285.1:n.831G>A
ENST00000682524.1:n.831G>A
ENST00000683738.1:n.831G>A
ENST00000355667.11:c.643G>A
ENST00000389253.9:c.643G>A
ENST00000355667.10:c.643G>A
ENST00000359692.10:c.643G>A
ENST00000389253.8:c.643G>A
ENST00000408974.8:c.643G>A
ENST00000585892.5:c.643G>A
ENST00000591701.5:n.3G>A
ENST00000591819.1:n.566G>A
NM_001005360.2:c.643G>A
NM_001005361.2:c.643G>A
NM_001005362.2:c.643G>A
NM_001190716.1:c.643G>A
NM_004945.3:c.643G>A
NM_001190716.2:c.643G>A
NM_001005360.3:c.643G>A
NM_001005362.3:c.643G>A
NM_004945.4:c.643G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 18
PVS1 PM5 PM4 PM1 PM2 BS2 BS3 BS1 BP7 BP3 BP4 BP1 PS4 PS1 PS3 PP4 PP3 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DNM2 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Congenital Myopathies VCEP
The variant NM_001005361.3:c.643G>A in DNM2 is a missense variant predicted to cause substitution of aspartic acid by asparagine at amino acid 215 (p.Asp215Asn). The filtering allele frequency (the lower threshold of the 95% CI of 10/6060) of the c.643G>A variant in DNM2 is 0.0009407 for Middle Eastern chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000015) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL predicts a score of 0.479 which is neither above nor below the thresholds predicting a damaging or benign impact on DNM2 function (PP3, BP4 not met). DNM2, in which the variant was identified, is defined by the ClinGen Congenital Myopathies VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2, not applied for this variant due to high allele frequency). In summary, this variant meets the criteria to be classified as benign for autosomal dominant centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1. (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024)
Met criteria codes
BA1
The filtering allele frequency (the lower threshold of the 95% CI of 10/6060) of the c.643G>A variant in DNM2 is 0.0009407 for Middle Eastern chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000015) for BA1, and therefore meets this criterion (BA1).
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
The computational predictor REVEL predicts a score of 0.479 which is neither above nor below the thresholds predicting a damaging or benign impact on DNM2 function (PP3, BP4 not met).
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
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
PP3
The computational predictor REVEL predicts a score of 0.479 which is neither above nor below the thresholds predicting a damaging or benign impact on DNM2 function (PP3, BP4 not met).
PP2
DNM2, in which the variant was identified, is defined by the ClinGen Congenital Myopathies VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2, not applied for this variant due to high allele frequency).
Curation History
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