2-71679041-T-C

Position:

chr2-71679041-T-C

Variant summary

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

The ENST00000410020.8(DYSF):c.5885-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,613,414 control chromosomes in the GnomAD database, including 644,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 63207 hom., cov: 31)

Exomes 𝑓: 0.89 ( 580944 hom. )

Consequence

DYSF
ENST00000410020.8 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.149

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 2-71679041-T-C is Benign according to our data. Variant chr2-71679041-T-C is described in ClinVar as [Benign]. Clinvar id is 94346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71679041-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 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.5885-16T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 linkuse as main transcript	c.5768-16T>C		splice_polypyrimidine_tract_variant, 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.5768-16T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003494.4	ENSP00000258104	A1	O75923-1
DYSF	ENST00000410020.8 linkuse as main transcript	c.5885-16T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001130987.2	ENSP00000386881	A1	O75923-13

Frequencies

GnomAD3 genomes

AF:

0.910

AC:

138379

AN:

152042

Hom.:

63163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.896

Gnomad OTH

AF:

0.908

GnomAD3 exomes

AF:

0.884

AC:

221974

AN:

251112

Hom.:

98426

AF XY:

0.881

AC XY:

119503

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.973

Gnomad AMR exome

AF:

0.908

Gnomad ASJ exome

AF:

0.879

Gnomad EAS exome

AF:

0.777

Gnomad SAS exome

AF:

0.835

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.895

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.891

AC:

1301681

AN:

1461254

Hom.:

580944

Cov.:

AF XY:

0.888

AC XY:

645721

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.972

Gnomad4 AMR exome

AF:

0.906

Gnomad4 ASJ exome

AF:

0.880

Gnomad4 EAS exome

AF:

0.730

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.899

Gnomad4 OTH exome

AF:

0.887

GnomAD4 genome

AF:

0.910

AC:

138479

AN:

152160

Hom.:

63207

Cov.:

AF XY:

0.907

AC XY:

67486

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.970

Gnomad4 AMR

AF:

0.915

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.758

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.896

Gnomad4 OTH

AF:

0.902

Alfa

AF:

0.894

Hom.:

85630

Bravo

AF:

0.916

Asia WGS

AF:

0.784

AC:

2727

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, 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)	Apr 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 25, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 12005/13006=92.3% -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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, 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

-0.89

CADD

Benign

9.0

DANN

Benign

0.45

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