Variant: NM_001164508.2(NEB):c.1015del (p.Ala339fs)

CA2499215129

1177402 (ClinVar)

Gene: NEB

Condition: nemaline myopathy

Inheritance Mode: Autosomal recessive inheritance

UUID: 69ff8498-d4df-49e2-93bf-eef0b1d63837

Approved on: 2024-08-27

Published on: 2025-03-27

HGVS expressions

NM_001164508.2:c.1015del
NM_001164508.2(NEB):c.1015del (p.Ala339fs)
NC_000002.12:g.151709676del
CM000664.2:g.151709676del
NC_000002.11:g.152566190del
CM000664.1:g.152566190del
NC_000002.10:g.152274436del
NG_009382.2:g.29812del
ENST00000397345.8:c.1015del
ENST00000427231.7:c.1015del
ENST00000172853.14:c.1015del
ENST00000397345.7:c.1015del
ENST00000409198.5:c.1015del
ENST00000427231.6:c.1015del
ENST00000603639.5:c.1015del
ENST00000604864.5:c.1015del
ENST00000618972.4:c.1015del
NM_001164507.1:c.1015del
NM_001164508.1:c.1015del
NM_001271208.1:c.1015del
NM_004543.4:c.1015del
NM_001271208.2:c.1015del
NM_004543.5:c.1015del
NM_001164507.2:c.1015del

Uncertain Significance

• Met criteria codes: PM2_Supporting PVS1

• Not Met criteria codes: BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS1 PS2 PS4 PS3 PP4 PP1 PP3 PP2 PM6 PM5 PM3 PM1 PM4

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

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

Evidence submitted by expert panel

Congenital Myopathies VCEP

The NM_001164508 c.1015del (p.Ala339fs) variant in NEB is a nonsense variant predicted to truncate the protein at amino acid 339 in exon 12 of 183 in NEB. Exon 12 is present in the biologically relevant transcript NM_001164508.2 and loss of function is a known mechanism of disease in NEB (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for Nemaline myopathy for autosomal recessive inheritance based on the ACMG/AMP criteria applied as specified by the ClinGen Congenital Myopathy VCEP: (PVS1, PM2_Supporting; ClinGen Congenital Myopathies VCEP Specifications version 1.0.0; 8/27/2024).

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD, ExAC, and 1000 Genomes
• PVS1: The NM_001164508.2(NEB):c.1015del p.(Ala339fs) variant results in a frameshift in exon 12 of 183 in NEB. Exon 12 is present in biologically relevant transcript NM_001164508.2. Loss of function is a known mechanism of disease.

Not Met criteria codes

• BA1: This variant is absent from gnomAD, ExAC, and 1000 Genomes
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: Functional studies for variant not found
• BS1: This variant is absent from gnomAD, ExAC, and 1000 Genomes
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: 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
• BP2: 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: Revel score unavailable
• 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
• PS2: De novo data not available
• PS4: Unable to find sufficient number of cases to invoke.
• PS3: Functional studies for variant not found
• PP4: No patient phenotype data available.
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: Revel score unavailable
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: De novo data not available
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: 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
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline