chr2-71552987-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130987.2(DYSF):c.1807-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,613,810 control chromosomes in the GnomAD database, including 2,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1071 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1754 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuromuscular disease caused by qualitative or quantitative defects of dysferlin
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
autosomal recessive limb-girdle muscular dystrophy type 2B
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
distal myopathy with anterior tibial onset
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myopathy, Paradas type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Miyoshi myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYSF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-71552987-C-G is Benign according to our data. Variant chr2-71552987-C-G is described in ClinVar as Benign. ClinVar VariationId is 259066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_001130987.2 link	c.1807-24C>G		intron_variant	Intron 19 of 55	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4 link	c.1753-24C>G		intron_variant	Intron 19 of 54	ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000410020.8 link	c.1807-24C>G		intron_variant	Intron 19 of 55	1	NM_001130987.2	ENSP00000386881.3
DYSF	ENST00000258104.8 link	c.1753-24C>G		intron_variant	Intron 19 of 54	1	NM_003494.4	ENSP00000258104.3

Frequencies

GnomAD3 genomes

AF:

0.0834

AC:

12692

AN:

152156

Hom.:

1071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.00913

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0311

Gnomad OTH

AF:

0.0735

GnomAD2 exomes

AF:

0.0434

AC:

10847

AN:

250010

AF XY:

0.0413

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.0230

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.0285

Gnomad FIN exome

AF:

0.00714

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0361

GnomAD4 exome

AF:

0.0361

AC:

52715

AN:

1461536

Hom.:

1754

Cov.:

AF XY:

0.0364

AC XY:

26480

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.229

AC:

7676

AN:

33470

American (AMR)

AF:

0.0257

AC:

1147

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

569

AN:

26128

East Asian (EAS)

AF:

0.0274

AC:

1089

AN:

39692

South Asian (SAS)

AF:

0.0582

AC:

5019

AN:

86216

European-Finnish (FIN)

AF:

0.00815

AC:

435

AN:

53354

Middle Eastern (MID)

AF:

0.0775

AC:

447

AN:

5768

European-Non Finnish (NFE)

AF:

0.0302

AC:

33539

AN:

1111828

Other (OTH)

AF:

0.0463

AC:

2794

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2473

4945

7418

9890

12363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0835

AC:

12715

AN:

152274

Hom.:

1071

Cov.:

AF XY:

0.0805

AC XY:

5993

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.221

AC:

9180

AN:

41514

American (AMR)

AF:

0.0403

AC:

616

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.0307

AC:

159

AN:

5178

South Asian (SAS)

AF:

0.0600

AC:

290

AN:

4830

European-Finnish (FIN)

AF:

0.00913

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0311

AC:

2117

AN:

68038

Other (OTH)

AF:

0.0737

AC:

156

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

554

1108

1662

2216

2770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0912

Asia WGS

AF:

0.0690

AC:

241

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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.

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

-0.82

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over