2-71598547-C-T

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.3575-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,614,046 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 227 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1207 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.11

Publications

2 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=-0.95).

BP6

Variant 2-71598547-C-T is Benign according to our data. Variant chr2-71598547-C-T is described in ClinVar as Benign. ClinVar VariationId is 94306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.3575-17C>T		intron_variant	Intron 32 of 55	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 link	c.3521-17C>T		intron_variant	Intron 32 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.3575-17C>T		intron_variant	Intron 32 of 55	1	NM_001130987.2	ENSP00000386881.3
DYSF	ENST00000258104.8 link	c.3521-17C>T		intron_variant	Intron 32 of 54	1	NM_003494.4	ENSP00000258104.3

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7253

AN:

152212

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0472

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0337

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0478

GnomAD2 exomes

AF:

0.0339

AC:

8479

AN:

250062

AF XY:

0.0332

show subpopulations

Gnomad AFR exome

AF:

0.0859

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0370

AC:

54091

AN:

1461716

Hom.:

1207

Cov.:

AF XY:

0.0369

AC XY:

26845

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0864

AC:

2892

AN:

33476

American (AMR)

AF:

0.0253

AC:

1131

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

1196

AN:

26134

East Asian (EAS)

AF:

0.000529

AC:

AN:

39690

South Asian (SAS)

AF:

0.0354

AC:

3056

AN:

86246

European-Finnish (FIN)

AF:

0.0129

AC:

690

AN:

53368

Middle Eastern (MID)

AF:

0.0609

AC:

351

AN:

5766

European-Non Finnish (NFE)

AF:

0.0381

AC:

42309

AN:

1111924

Other (OTH)

AF:

0.0405

AC:

2445

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2802

5604

8406

11208

14010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1604

3208

4812

6416

8020

<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:

0.0477

AC:

7263

AN:

152330

Hom.:

227

Cov.:

AF XY:

0.0451

AC XY:

3357

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0836

AC:

3474

AN:

41576

American (AMR)

AF:

0.0352

AC:

539

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

164

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0344

AC:

166

AN:

4830

European-Finnish (FIN)

AF:

0.0129

AC:

137

AN:

10624

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0388

AC:

2642

AN:

68026

Other (OTH)

AF:

0.0473

AC:

100

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

353

706

1059

1412

1765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0227

Hom.:

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 02, 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.

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 29, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

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

-0.95

CADD

Benign

0.066

(source)

DANN

Benign

0.63

PhyloP100

-2.1

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