rs115184725

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001130987.2(DYSF):c.889-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,603,320 control chromosomes in the GnomAD database, including 556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 49 hom., cov: 33)

Exomes 𝑓: 0.024 ( 507 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.57

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=-0.87).

BP6

Variant 2-71516146-C-T is Benign according to our data. Variant chr2-71516146-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71516146-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2833/152348) while in subpopulation NFE AF= 0.0277 (1886/68036). AF 95% confidence interval is 0.0267. There are 49 homozygotes in gnomad4. There are 1337 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYSF	NM_001130987.2 linkuse as main transcript	c.889-34C>T		intron_variant		ENST00000410020.8
DYSF	NM_003494.4 linkuse as main transcript	c.793-34C>T		intron_variant		ENST00000258104.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYSF	ENST00000258104.8 linkuse as main transcript	c.793-34C>T		intron_variant		1	NM_003494.4	A1	O75923-1
DYSF	ENST00000410020.8 linkuse as main transcript	c.889-34C>T		intron_variant		1	NM_001130987.2	A1	O75923-13

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2833

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0200

AC:

5030

AN:

251322

Hom.:

AF XY:

0.0206

AC XY:

2792

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0584

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00866

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0243

AC:

35295

AN:

1450972

Hom.:

507

Cov.:

AF XY:

0.0241

AC XY:

17377

AN XY:

722466

show subpopulations

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00889

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0271

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0186

AC:

2833

AN:

152348

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1337

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00459

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0275

Hom.:

Bravo

AF:

0.0182

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Miyoshi muscular dystrophy 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

1.7

Dann

Benign

0.64

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