Evidence Repository - Clinical Genome Resources

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_001005361.3(DNM2):c.2484G>A (p.Pro828=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA172130

158526 (ClinVar)

Gene: DNM2

Condition: centronuclear myopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 412535a5-8c56-4c49-b9b8-0e5e339ff824

Approved on: 2024-08-07

Published on: 2024-10-01

HGVS expressions

NM_001005361.3:c.2484G>A

NM_001005361.3(DNM2):c.2484G>A (p.Pro828=)

NC_000019.10:g.10830319G>A

CM000681.2:g.10830319G>A

NC_000019.9:g.10940995G>A

CM000681.1:g.10940995G>A

NC_000019.8:g.10801995G>A

NG_008792.1:g.117241G>A

ENST00000681972.1:n.1915G>A

ENST00000355667.11:c.2484G>A

ENST00000389253.9:c.2484G>A

ENST00000355667.10:c.2484G>A

ENST00000359692.10:c.2472G>A

ENST00000389253.8:c.2484G>A

ENST00000408974.8:c.2472G>A

ENST00000585892.5:c.2484G>A

ENST00000589106.1:c.350G>A

ENST00000590806.5:n.4672G>A

ENST00000593203.1:n.1267G>A

NM_001005360.2:c.2484G>A

NM_001005361.2:c.2484G>A

NM_001005362.2:c.2472G>A

NM_001190716.1:c.2484G>A

NM_004945.3:c.2472G>A

NM_001190716.2:c.2484G>A

NM_001005360.3:c.2484G>A

NM_001005362.3:c.2472G>A

NM_004945.4:c.2472G>A

Benign

BA1 BP7 BP4

PM2 BS1

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

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.2484G>A in DNM2 is a synonymous (silent) variant (p.Pro828=). The filtering allele frequency (the lower threshold of the 95% CI of 2652/74982) of the c.2484G>A variant in DNM2 is 0.03445 for African/African American 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 c.2484G>A (p.Pro828=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). 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, BP4, BP7. (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024)

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 2652/74982) of the c.2484G>A variant in DNM2 is 0.03445 for African/African American 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).

BP7

SpliceAi provided values of 0.01 for Acceptor loss and gain, and 0.00 for donor loss and gain, and therefore does not predict that the variant impacts splicing.

BP4

SpliceAi provided values of 0.01 for Acceptor loss and gain, and 0.00 for donor loss and gain, and therefore does not predict that the variant impacts splicing.

PM2

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

Curation History

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