rs13424178

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1985-31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 674,188 control chromosomes in the GnomAD database, including 2,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 144 hom., cov: 29)

Exomes 𝑓: 0.13 ( 2068 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.964

Publications

1 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=-0.81).

BP6

Variant 2-71553776-C-A is Benign according to our data. Variant chr2-71553776-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.1985-31C>A		intron_variant	Intron 20 of 55	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 link	c.1931-31C>A		intron_variant	Intron 20 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.1985-31C>A		intron_variant	Intron 20 of 55	1	NM_001130987.2	ENSP00000386881.3
DYSF	ENST00000258104.8 link	c.1931-31C>A		intron_variant	Intron 20 of 54	1	NM_003494.4	ENSP00000258104.3

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

5531

AN:

134268

Hom.:

144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.0654

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.000276

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0563

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0440

GnomAD2 exomes

AF:

0.0363

AC:

8002

AN:

220410

AF XY:

0.0376

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.000181

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.129

AC:

69530

AN:

539826

Hom.:

2068

Cov.:

AF XY:

0.119

AC XY:

34147

AN XY:

287344

show subpopulations

African (AFR)

AF:

0.0403

AC:

493

AN:

12220

American (AMR)

AF:

0.0239

AC:

835

AN:

34870

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

2453

AN:

14312

East Asian (EAS)

AF:

0.0000771

AC:

AN:

12978

South Asian (SAS)

AF:

0.0457

AC:

3015

AN:

65908

European-Finnish (FIN)

AF:

0.0322

AC:

1022

AN:

31772

Middle Eastern (MID)

AF:

0.0782

AC:

244

AN:

3122

European-Non Finnish (NFE)

AF:

0.171

AC:

58500

AN:

342042

Other (OTH)

AF:

0.131

AC:

2967

AN:

22602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2863

5726

8589

11452

14315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2286

4572

6858

9144

11430

<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:

0.0412

AC:

5534

AN:

134362

Hom.:

144

Cov.:

AF XY:

0.0393

AC XY:

2525

AN XY:

64246

show subpopulations

African (AFR)

AF:

0.0206

AC:

755

AN:

36622

American (AMR)

AF:

0.0398

AC:

511

AN:

12834

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

345

AN:

3290

East Asian (EAS)

AF:

0.000276

AC:

AN:

3628

South Asian (SAS)

AF:

0.0443

AC:

164

AN:

3702

European-Finnish (FIN)

AF:

0.0241

AC:

183

AN:

7596

Middle Eastern (MID)

AF:

0.0679

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0537

AC:

3415

AN:

63610

Other (OTH)

AF:

0.0436

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

242

484

726

968

1210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0318

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Likely 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.

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.75

PhyloP100

0.96

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