2-71515762-T-C

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.888+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,846 control chromosomes in the GnomAD database, including 14,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1378 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13275 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.467

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=-0.89).

BP6

Variant 2-71515762-T-C is Benign according to our data. Variant chr2-71515762-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 94361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71515762-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.888+11T>C		intron_variant	Intron 8 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.792+11T>C		intron_variant	Intron 7 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.888+11T>C		intron_variant	Intron 8 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.792+11T>C		intron_variant	Intron 7 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20123

AN:

151996

Hom.:

1374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0297

Gnomad SAS

AF:

0.0817

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.115

AC:

28795

AN:

251150

Hom.:

1778

AF XY:

0.115

AC XY:

15617

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.0298

Gnomad SAS exome

AF:

0.0875

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.131

AC:

192192

AN:

1461732

Hom.:

13275

Cov.:

AF XY:

0.130

AC XY:

94538

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0786

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.0248

Gnomad4 SAS exome

AF:

0.0911

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.133

AC:

20156

AN:

152114

Hom.:

1378

Cov.:

AF XY:

0.132

AC XY:

9810

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0297

Gnomad4 SAS

AF:

0.0814

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.125

Hom.:

838

Bravo

AF:

0.130

Asia WGS

AF:

0.0510

AC:

180

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Jan 29, 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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 24, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.888+11T>C in intron 8 of DYSF: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 14.9% (656/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs13428076). -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Qualitative or quantitative defects of dysferlin

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely 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: Likely 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

- -

Miyoshi myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely 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

-0.89

CADD

Benign

4.8

DANN

Benign

0.56

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