rs11558179

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001130987.2(DYSF):c.4026C>T(p.Asn1342Asn) 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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuromuscular disease caused by qualitative or quantitative defects of dysferlin
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
autosomal recessive limb-girdle muscular dystrophy type 2B
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
distal myopathy with anterior tibial onset
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myopathy, Paradas type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Miyoshi myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYSF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 94314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.4026C>T	p.Asn1342Asn	synonymous_variant	Exon 37 of 56	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.3972C>T	p.Asn1324Asn	synonymous_variant	Exon 37 of 55	ENST00000258104.8	NP_003485.1	O75923-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000410020.8 link	c.4026C>T	p.Asn1342Asn	synonymous_variant	Exon 37 of 56	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.3972C>T	p.Asn1324Asn	synonymous_variant	Exon 37 of 55	1	NM_003494.4	ENSP00000258104.3		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

GnomAD2 exomes

AF:

0.0867

AC:

21738

AN:

250610

AF XY:

0.0772

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 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

African (AFR)

AF:

0.493

AC:

16491

AN:

33474

American (AMR)

AF:

0.0942

AC:

4210

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0846

AC:

2211

AN:

26128

East Asian (EAS)

AF:

0.0469

AC:

1862

AN:

39700

South Asian (SAS)

AF:

0.0537

AC:

4634

AN:

86250

European-Finnish (FIN)

AF:

0.0485

AC:

2589

AN:

53396

Middle Eastern (MID)

AF:

0.0832

AC:

480

AN:

5768

European-Non Finnish (NFE)

AF:

0.0515

AC:

57216

AN:

1111718

Other (OTH)

AF:

0.0812

AC:

4904

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5035

10071

15106

20142

25177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2356

4712

7068

9424

11780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26796

AN:

152142

Hom.:

5026

Cov.:

AF XY:

0.173

AC XY:

12870

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.478

AC:

19806

AN:

41448

American (AMR)

AF:

0.117

AC:

1790

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

262

AN:

3472

East Asian (EAS)

AF:

0.0383

AC:

198

AN:

5166

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4826

European-Finnish (FIN)

AF:

0.0455

AC:

483

AN:

10618

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0531

AC:

3608

AN:

67998

Other (OTH)

AF:

0.137

AC:

289

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

854

1708

2563

3417

4271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0850

Hom.:

4397

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 22, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 06, 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive limb-girdle muscular dystrophy type 2B

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Miyoshi muscular dystrophy 1

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Miyoshi myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

(source)

DANN

Benign

0.85

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over