Variant: NM_001005361.3(DNM2):c.654C>T (p.Asp218=)

CA9200851

1151351 (ClinVar)

Gene: DNM2

Condition: centronuclear myopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: edcd3add-9d50-47ca-9585-ea6aab076716

Approved on: 2024-08-07

Published on: 2024-10-01

HGVS expressions

NM_001005361.3:c.654C>T
NM_001005361.3(DNM2):c.654C>T (p.Asp218=)
NC_000019.10:g.10777182C>T
CM000681.2:g.10777182C>T
NC_000019.9:g.10887858C>T
CM000681.1:g.10887858C>T
NC_000019.8:g.10748858C>T
NG_008792.1:g.64104C>T
ENST00000682285.1:n.842C>T
ENST00000682524.1:n.842C>T
ENST00000683738.1:n.842C>T
ENST00000355667.11:c.654C>T
ENST00000389253.9:c.654C>T
ENST00000355667.10:c.654C>T
ENST00000359692.10:c.654C>T
ENST00000389253.8:c.654C>T
ENST00000408974.8:c.654C>T
ENST00000585892.5:c.654C>T
ENST00000591701.5:n.14C>T
ENST00000591819.1:n.577C>T
NM_001005360.2:c.654C>T
NM_001005361.2:c.654C>T
NM_001005362.2:c.654C>T
NM_001190716.1:c.654C>T
NM_004945.3:c.654C>T
NM_001190716.2:c.654C>T
NM_001005360.3:c.654C>T
NM_001005362.3:c.654C>T
NM_004945.4:c.654C>T

Benign

• Met criteria codes: BA1 BP7 BP4

• Not Met criteria codes: BS3 BS1 BP3 BP1 PS1 PS3 PP4 PP3 PP2 PM2 PM4 PM5 PM1 PVS1

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

Evidence submitted by expert panel

Congenital Myopathies VCEP

The variant NM_001005361.3:c.654C>T is a synonymous (silent) variant (p.Asp218=) in exon 5/21 of DNM2. The filtering allele frequency (the lower threshold of the 95% CI of 29/1180014) of the c.654C>T variant in DNM2 is 0.00001663 for European (non-Finnish) 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.654C>T (p.Asp218=) 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)

Met criteria codes

• BA1: The filtering allele frequency (the lower threshold of the 95% CI of 29/1180014) of the c.654C>T variant in DNM2 is 0.00001663 for European (non-Finnish) 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 predicts no impact on splicing
• BP4: SpliceAI predicts no impact on splicing

Not Met criteria codes

• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000015) for BA1, and therefore meets this criterion (BA1).
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: 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: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.0000015) for BA1, and therefore meets this criterion (BA1).
• PM4: 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
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline