chr2-71611313-C-T

Position:

chr2-71611313-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001130987.2(DYSF):c.4026C>T(p.Asn1342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,613,634 control chromosomes in the GnomAD database, including 11,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 5026 hom., cov: 32)

Exomes 𝑓: 0.065 ( 6594 hom. )

Consequence

DYSF
NM_001130987.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.313

Variant links:

Genes affected

DYSF (HGNC:3097): (dysferlin) The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]

DYSF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-71611313-C-T is Benign according to our data. Variant chr2-71611313-C-T is described in ClinVar as [Benign]. Clinvar id is 94314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71611313-C-T is described in Lovd as [Benign]. Variant chr2-71611313-C-T is described in Lovd as [Likely_pathogenic].

BP7

Synonymous conserved (PhyloP=-0.313 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYSF	NM_001130987.2 linkuse as main transcript	c.4026C>T	p.Asn1342=	synonymous_variant	37/56	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 linkuse as main transcript	c.3972C>T	p.Asn1324=	synonymous_variant	37/55	ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000410020.8 linkuse as main transcript	c.4026C>T	p.Asn1342=	synonymous_variant	37/56	1	NM_001130987.2	ENSP00000386881	A1	O75923-13
DYSF	ENST00000258104.8 linkuse as main transcript	c.3972C>T	p.Asn1324=	synonymous_variant	37/55	1	NM_003494.4	ENSP00000258104	A1	O75923-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26729

AN:

152024

Hom.:

5006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.0384

Gnomad SAS

AF:

0.0551

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.0867

AC:

21738

AN:

250610

Hom.:

2383

AF XY:

0.0772

AC XY:

10454

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.0933

Gnomad ASJ exome

AF:

0.0830

Gnomad EAS exome

AF:

0.0365

Gnomad SAS exome

AF:

0.0539

Gnomad FIN exome

AF:

0.0435

Gnomad NFE exome

AF:

0.0531

Gnomad OTH exome

AF:

0.0792

GnomAD4 exome

AF:

0.0647

AC:

94597

AN:

1461492

Hom.:

6594

Cov.:

AF XY:

0.0625

AC XY:

45436

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.0942

Gnomad4 ASJ exome

AF:

0.0846

Gnomad4 EAS exome

AF:

0.0469

Gnomad4 SAS exome

AF:

0.0537

Gnomad4 FIN exome

AF:

0.0485

Gnomad4 NFE exome

AF:

0.0515

Gnomad4 OTH exome

AF:

0.0812

GnomAD4 genome

AF:

0.176

AC:

26796

AN:

152142

Hom.:

5026

Cov.:

AF XY:

0.173

AC XY:

12870

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.0383

Gnomad4 SAS

AF:

0.0545

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0531

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.0736

Hom.:

1562

Bravo

AF:

0.194

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.0547

EpiControl

AF:

0.0533

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 22, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Asn1342Asn in exon 37 of DYSF: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 47.0% (2072/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11558179). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Qualitative or quantitative defects of dysferlin

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive limb-girdle muscular dystrophy type 2B

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Miyoshi muscular dystrophy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Miyoshi myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

DANN

Benign

0.85

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