2-71679041-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130987.2(DYSF):c.5885-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,613,414 control chromosomes in the GnomAD database, including 644,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 63207 hom., cov: 31)

Exomes 𝑓: 0.89 ( 580944 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.149

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-71679041-T-C is Benign according to our data. Variant chr2-71679041-T-C is described in ClinVar as Benign. ClinVar VariationId is 94346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.5885-16T>C		intron_variant	Intron 52 of 55	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 link	c.5768-16T>C		intron_variant	Intron 51 of 54	ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000410020.8 link	c.5885-16T>C		intron_variant	Intron 52 of 55	1	NM_001130987.2	ENSP00000386881.3
DYSF	ENST00000258104.8 link	c.5768-16T>C		intron_variant	Intron 51 of 54	1	NM_003494.4	ENSP00000258104.3

Frequencies

GnomAD3 genomes

AF:

0.910

AC:

138379

AN:

152042

Hom.:

63163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.896

Gnomad OTH

AF:

0.908

GnomAD2 exomes

AF:

0.884

AC:

221974

AN:

251112

AF XY:

0.881

show subpopulations

Gnomad AFR exome

AF:

0.973

Gnomad AMR exome

AF:

0.908

Gnomad ASJ exome

AF:

0.879

Gnomad EAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.895

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.891

AC:

1301681

AN:

1461254

Hom.:

580944

Cov.:

AF XY:

0.888

AC XY:

645721

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.972

AC:

32525

AN:

33468

American (AMR)

AF:

0.906

AC:

40516

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

22984

AN:

26130

East Asian (EAS)

AF:

0.730

AC:

28976

AN:

39694

South Asian (SAS)

AF:

0.835

AC:

72033

AN:

86230

European-Finnish (FIN)

AF:

0.884

AC:

47212

AN:

53412

Middle Eastern (MID)

AF:

0.897

AC:

5120

AN:

5710

European-Non Finnish (NFE)

AF:

0.899

AC:

998785

AN:

1111540

Other (OTH)

AF:

0.887

AC:

53530

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7356

14713

22069

29426

36782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21414

42828

64242

85656

107070

<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:

0.910

AC:

138479

AN:

152160

Hom.:

63207

Cov.:

AF XY:

0.907

AC XY:

67486

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.970

AC:

40295

AN:

41524

American (AMR)

AF:

0.915

AC:

14005

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

3037

AN:

3470

East Asian (EAS)

AF:

0.758

AC:

3885

AN:

5124

South Asian (SAS)

AF:

0.828

AC:

3992

AN:

4820

European-Finnish (FIN)

AF:

0.888

AC:

9414

AN:

10606

Middle Eastern (MID)

AF:

0.908

AC:

265

AN:

292

European-Non Finnish (NFE)

AF:

0.896

AC:

60900

AN:

67992

Other (OTH)

AF:

0.902

AC:

1907

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

620

1240

1861

2481

3101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.897

Hom.:

107335

Bravo

AF:

0.916

Asia WGS

AF:

0.784

AC:

2727

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Apr 24, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 05, 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. -

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 12005/13006=92.3% -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Distal myopathy with anterior tibial onset

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

9.0

(source)

DANN

Benign

0.45

PhyloP100

0.15

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

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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