NM_001130987.2:c.1277-48A>G

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.1277-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,536,098 control chromosomes in the GnomAD database, including 497,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 50265 hom., cov: 32)

Exomes 𝑓: 0.80 ( 447632 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0510

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=-0.9).

BP6

Variant 2-71528250-A-G is Benign according to our data. Variant chr2-71528250-A-G is described in ClinVar as [Benign]. Clinvar id is 259065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71528250-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.1277-48A>G		intron_variant	Intron 13 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.1181-48A>G		intron_variant	Intron 12 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.1277-48A>G		intron_variant	Intron 13 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.1181-48A>G		intron_variant	Intron 12 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121834

AN:

152072

Hom.:

50212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.821

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.777

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.806

GnomAD3 exomes

AF:

0.733

AC:

166725

AN:

227464

Hom.:

64909

AF XY:

0.731

AC XY:

89120

AN XY:

121940

show subpopulations

Gnomad AFR exome

AF:

0.885

Gnomad AMR exome

AF:

0.685

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.589

Gnomad FIN exome

AF:

0.779

Gnomad NFE exome

AF:

0.832

Gnomad OTH exome

AF:

0.774

GnomAD4 exome

AF:

0.795

AC:

1100315

AN:

1383908

Hom.:

447632

Cov.:

AF XY:

0.790

AC XY:

545399

AN XY:

690732

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.697

Gnomad4 ASJ exome

AF:

0.859

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.785

Gnomad4 NFE exome

AF:

0.833

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.801

AC:

121948

AN:

152190

Hom.:

50265

Cov.:

AF XY:

0.788

AC XY:

58659

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.732

Gnomad4 ASJ

AF:

0.859

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.551

Gnomad4 FIN

AF:

0.777

Gnomad4 NFE

AF:

0.828

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.823

Hom.:

10640

Bravo

AF:

0.803

Asia WGS

AF:

0.429

AC:

1496

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: 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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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