2-151727790-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001164508.2(NEB):c.195G>A(p.Pro65Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,612,994 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 46 hom. )

Consequence

NEB
NM_001164508.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.88

Variant links:

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-151727790-C-T is Benign according to our data. Variant chr2-151727790-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 95125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1926/152252) while in subpopulation AFR AF= 0.0442 (1836/41550). AF 95% confidence interval is 0.0425. There are 45 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 5 of 182	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 5 of 182	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEB	ENST00000397345.8 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 5 of 182	5	NM_001164508.2	ENSP00000380505.3	P20929-2
NEB	ENST00000427231.7 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 5 of 182	5	NM_001164507.2	ENSP00000416578.2	P20929-3
NEB	ENST00000409198.5 link	c.195G>A	p.Pro65Pro	synonymous_variant	Exon 5 of 150	5		ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1923

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00351

AC:

872

AN:

248574

Hom.:

AF XY:

0.00274

AC XY:

370

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.0473

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00146

AC:

2137

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

946

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.00251

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000837

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.0127

AC:

1926

AN:

152252

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

906

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0442

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00441

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 11, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 19, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nemaline myopathy 2

Benign:3

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.52

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over