2-71598547-C-T

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.3575-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,614,046 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 227 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1207 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.11

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=-0.95).

BP6

Variant 2-71598547-C-T is Benign according to our data. Variant chr2-71598547-C-T is described in ClinVar as [Benign]. Clinvar id is 94306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71598547-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.3575-17C>T		intron_variant	Intron 32 of 55	ENST00000410020.8	NP_001124459.1	O75923-13
DYSF	NM_003494.4 link	c.3521-17C>T		intron_variant	Intron 32 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.3575-17C>T		intron_variant	Intron 32 of 55	1	NM_001130987.2	ENSP00000386881.3		O75923-13
DYSF	ENST00000258104.8 link	c.3521-17C>T		intron_variant	Intron 32 of 54	1	NM_003494.4	ENSP00000258104.3		O75923-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7253

AN:

152212

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0472

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0337

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0339

AC:

8479

AN:

250062

Hom.:

206

AF XY:

0.0332

AC XY:

4498

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.0859

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0342

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0370

AC:

54091

AN:

1461716

Hom.:

1207

Cov.:

AF XY:

0.0369

AC XY:

26845

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0864

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0405

GnomAD4 genome

AF:

0.0477

AC:

7263

AN:

152330

Hom.:

227

Cov.:

AF XY:

0.0451

AC XY:

3357

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.0352

Gnomad4 ASJ

AF:

0.0472

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0344

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.0388

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0208

Hom.:

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 02, 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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 29, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Significance: Likely benign

Review Status: no assertion criteria provided

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

- -

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

-0.95

CADD

Benign

0.066

DANN

Benign

0.63

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