rs111935215

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_StrongBS1BS2

The NM_001130987.2(DYSF):c.4222-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,612,970 control chromosomes in the GnomAD database, including 642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 56 hom., cov: 33)

Exomes 𝑓: 0.025 ( 586 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.696

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 2-71612621-G-A is Benign according to our data. Variant chr2-71612621-G-A is described in ClinVar as [Benign]. Clinvar id is 94319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71612621-G-A is described in Lovd as [Benign]. Variant chr2-71612621-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0247 (3757/152322) while in subpopulation SAS AF= 0.0425 (205/4828). AF 95% confidence interval is 0.0377. There are 56 homozygotes in gnomad4. There are 1815 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.4222-20G>A		intron_variant	Intron 38 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.4168-20G>A		intron_variant	Intron 38 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.4222-20G>A		intron_variant	Intron 38 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.4168-20G>A		intron_variant	Intron 38 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3753

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0662

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0428

Gnomad FIN

AF:

0.00876

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0236

AC:

5920

AN:

250586

Hom.:

108

AF XY:

0.0251

AC XY:

3400

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0731

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0248

AC:

36185

AN:

1460648

Hom.:

586

Cov.:

AF XY:

0.0253

AC XY:

18354

AN XY:

726362

show subpopulations

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.0752

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0429

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0277

GnomAD4 genome

AF:

0.0247

AC:

3757

AN:

152322

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.0206

Gnomad4 ASJ

AF:

0.0662

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0425

Gnomad4 FIN

AF:

0.00876

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0301

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 19, 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

- -

Mar 04, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.89

CADD

Benign

0.12

DANN

Benign

0.49

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