chr2-71515606-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 94356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71515606-C-T is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.0766

AC:

19231

AN:

251094

Hom.:

1071

AF XY:

0.0755

AC XY:

10248

AN XY:

135764

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 SAS exome

AF:

0.0463

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

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.0574

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.0477

Gnomad4 FIN exome

AF:

0.0460

Gnomad4 NFE exome

AF:

0.0874

Gnomad4 OTH exome

AF:

0.0841

GnomAD4 genome

AF:

0.113

AC:

17233

AN:

152106

Hom.:

1303

Cov.:

AF XY:

0.108

AC XY:

8059

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.0852

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.00483

Gnomad4 SAS

AF:

0.0438

Gnomad4 FIN

AF:

0.0421

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.106

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

- -

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.40

DANN

Benign

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over