rs61104194

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.760-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,613,696 control chromosomes in the GnomAD database, including 7,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1303 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5756 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.899

Publications

5 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=-0.87).

BP6

Variant 2-71515606-C-T is Benign according to our data. Variant chr2-71515606-C-T is described in ClinVar as Benign. ClinVar VariationId is 94356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.760-17C>T		intron_variant	Intron 7 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.664-17C>T		intron_variant	Intron 6 of 54	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.760-17C>T		intron_variant	Intron 7 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.664-17C>T		intron_variant	Intron 6 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17213

AN:

151988

Hom.:

1300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0854

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00463

Gnomad SAS

AF:

0.0442

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0897

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0766

AC:

19231

AN:

251094

AF XY:

0.0755

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0589

Gnomad EAS exome

AF:

0.00217

Gnomad FIN exome

AF:

0.0461

Gnomad NFE exome

AF:

0.0919

Gnomad OTH exome

AF:

0.0825

GnomAD4 exome

AF:

0.0826

AC:

120774

AN:

1461590

Hom.:

5756

Cov.:

AF XY:

0.0814

AC XY:

59196

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.216

AC:

7226

AN:

33468

American (AMR)

AF:

0.0574

AC:

2566

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1536

AN:

26130

East Asian (EAS)

AF:

0.00194

AC:

AN:

39696

South Asian (SAS)

AF:

0.0477

AC:

4112

AN:

86250

European-Finnish (FIN)

AF:

0.0460

AC:

2456

AN:

53394

Middle Eastern (MID)

AF:

0.0942

AC:

543

AN:

5762

European-Non Finnish (NFE)

AF:

0.0874

AC:

97178

AN:

1111800

Other (OTH)

AF:

0.0841

AC:

5080

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

6117

12234

18352

24469

30586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3534

7068

10602

14136

17670

<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:

0.113

AC:

17233

AN:

152106

Hom.:

1303

Cov.:

AF XY:

0.108

AC XY:

8059

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.209

AC:

8644

AN:

41440

American (AMR)

AF:

0.0852

AC:

1303

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.00483

AC:

AN:

5174

South Asian (SAS)

AF:

0.0438

AC:

211

AN:

4812

European-Finnish (FIN)

AF:

0.0421

AC:

446

AN:

10606

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0896

AC:

6095

AN:

67988

Other (OTH)

AF:

0.106

AC:

223

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

737

1474

2212

2949

3686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0903

Hom.:

136

Bravo

AF:

0.121

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 24, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 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. -

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

- -

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

- -

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

- -

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

-0.87

CADD

Benign

0.40

(source)

DANN

Benign

0.37

PhyloP100

-0.90

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