rs3764971

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130987.2(DYSF):c.3086-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,611,560 control chromosomes in the GnomAD database, including 50,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3894 hom., cov: 33)

Exomes 𝑓: 0.25 ( 46542 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.455

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=-0.92).

BP6

Variant 2-71570582-G-A is Benign according to our data. Variant chr2-71570582-G-A is described in ClinVar as [Benign]. Clinvar id is 94297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71570582-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.3086-17G>A		intron_variant	Intron 28 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.3032-17G>A		intron_variant	Intron 28 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.3086-17G>A		intron_variant	Intron 28 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.3032-17G>A		intron_variant	Intron 28 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30552

AN:

152062

Hom.:

3888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.259

AC:

63891

AN:

246488

Hom.:

9445

AF XY:

0.266

AC XY:

35443

AN XY:

133372

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.453

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.245

AC:

357986

AN:

1459380

Hom.:

46542

Cov.:

AF XY:

0.249

AC XY:

180587

AN XY:

725894

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.419

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.201

AC:

30551

AN:

152180

Hom.:

3894

Cov.:

AF XY:

0.209

AC XY:

15561

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0618

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.449

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.217

Hom.:

2149

Bravo

AF:

0.192

Asia WGS

AF:

0.372

AC:

1292

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Apr 08, 2013

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 18, 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. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

-0.92

CADD

Benign

4.7

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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