Variant 2-71520250-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001130987.2(DYSF):c.1033+43delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,612,022 control chromosomes in the GnomAD database, including 1,994 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 124 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1870 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.204

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 -16 ACMG points.

BP6

Variant 2-71520250-CT-C is Benign according to our data. Variant chr2-71520250-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 259088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71520250-CT-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.1033+43delT		intron_variant	Intron 11 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.937+43delT		intron_variant	Intron 10 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.1033+43delT		intron_variant	Intron 11 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.937+43delT		intron_variant	Intron 10 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5516

AN:

152172

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0873

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0349

AC:

8774

AN:

251478

Hom.:

188

AF XY:

0.0359

AC XY:

4882

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0861

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0345

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0454

Gnomad OTH exome

AF:

0.0396

GnomAD4 exome

AF:

0.0468

AC:

68387

AN:

1459734

Hom.:

1870

Cov.:

AF XY:

0.0464

AC XY:

33679

AN XY:

726390

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0887

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.0514

Gnomad4 OTH exome

AF:

0.0495

GnomAD4 genome

AF:

0.0363

AC:

5522

AN:

152288

Hom.:

124

Cov.:

AF XY:

0.0342

AC XY:

2544

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0873

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0350

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0478

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0248

Hom.:

Bravo

AF:

0.0366

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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