chr2-71520769-G-A

Position:

chr2-71520769-G-A

Variant summary

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

The NM_001130987.2(DYSF):c.1034-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,609,198 control chromosomes in the GnomAD database, including 216,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18082 hom., cov: 31)

Exomes 𝑓: 0.51 ( 198112 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.11

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 2-71520769-G-A is Benign according to our data. Variant chr2-71520769-G-A is described in ClinVar as [Benign]. Clinvar id is 94368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71520769-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYSF	NM_001130987.2 linkuse as main transcript	c.1034-20G>A		intron_variant		ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 linkuse as main transcript	c.938-20G>A		intron_variant		ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000258104.8 linkuse as main transcript	c.938-20G>A		intron_variant		1	NM_003494.4	ENSP00000258104	A1	O75923-1
DYSF	ENST00000410020.8 linkuse as main transcript	c.1034-20G>A		intron_variant		1	NM_001130987.2	ENSP00000386881	A1	O75923-13

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72615

AN:

151778

Hom.:

18069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.495

GnomAD3 exomes

AF:

0.479

AC:

120394

AN:

251342

Hom.:

30984

AF XY:

0.478

AC XY:

64899

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.590

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.536

Gnomad OTH exome

AF:

0.507

GnomAD4 exome

AF:

0.515

AC:

749790

AN:

1457302

Hom.:

198112

Cov.:

AF XY:

0.512

AC XY:

371145

AN XY:

725330

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.526

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.478

AC:

72676

AN:

151896

Hom.:

18082

Cov.:

AF XY:

0.472

AC XY:

35039

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.411

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.587

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.547

Gnomad4 NFE

AF:

0.534

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.519

Hom.:

7081

Bravo

AF:

0.474

Asia WGS

AF:

0.254

AC:

888

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 29, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Distal myopathy with anterior tibial onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive limb-girdle muscular dystrophy type 2B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Miyoshi muscular dystrophy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Qualitative or quantitative defects of dysferlin

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0020

DANN

Benign

0.38

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