rs84182

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.4626+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,501,960 control chromosomes in the GnomAD database, including 570,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57360 hom., cov: 31)

Exomes 𝑓: 0.87 ( 512949 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.13

Publications

7 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=-0.89).

BP6

Variant 2-71644106-A-G is Benign according to our data. Variant chr2-71644106-A-G is described in ClinVar as Benign. ClinVar VariationId is 259080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130987.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYSF	NM_001130987.2	MANE Select	c.4626+43A>G	intron	N/A	NP_001124459.1	O75923-13
DYSF	NM_003494.4	MANE Plus Clinical	c.4509+43A>G	intron	N/A	NP_003485.1	O75923-1
DYSF	NM_001130981.2		c.4623+43A>G	intron	N/A	NP_001124453.1	O75923-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYSF	ENST00000410020.8	TSL:1 MANE Select	c.4626+43A>G	intron	N/A	ENSP00000386881.3	O75923-13
DYSF	ENST00000258104.8	TSL:1 MANE Plus Clinical	c.4509+43A>G	intron	N/A	ENSP00000258104.3	O75923-1
DYSF	ENST00000409582.7	TSL:1	c.4623+43A>G	intron	N/A	ENSP00000386547.3	O75923-7

Frequencies

GnomAD3 genomes

AF:

0.867

AC:

131840

AN:

152038

Hom.:

57324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.789

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.876

Gnomad OTH

AF:

0.857

GnomAD2 exomes

AF:

0.845

AC:

170153

AN:

201330

AF XY:

0.850

show subpopulations

Gnomad AFR exome

AF:

0.900

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.859

Gnomad NFE exome

AF:

0.881

Gnomad OTH exome

AF:

0.850

GnomAD4 exome

AF:

0.871

AC:

1175651

AN:

1349804

Hom.:

512949

Cov.:

AF XY:

0.871

AC XY:

585829

AN XY:

672776

show subpopulations

African (AFR)

AF:

0.898

AC:

28187

AN:

31390

American (AMR)

AF:

0.720

AC:

28655

AN:

39824

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

21425

AN:

24982

East Asian (EAS)

AF:

0.788

AC:

30254

AN:

38388

South Asian (SAS)

AF:

0.848

AC:

68190

AN:

80416

European-Finnish (FIN)

AF:

0.857

AC:

44002

AN:

51330

Middle Eastern (MID)

AF:

0.911

AC:

4620

AN:

5074

European-Non Finnish (NFE)

AF:

0.882

AC:

901368

AN:

1021840

Other (OTH)

AF:

0.865

AC:

48950

AN:

56560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8059

16118

24178

32237

40296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19296

38592

57888

77184

96480

<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:

0.867

AC:

131925

AN:

152156

Hom.:

57360

Cov.:

AF XY:

0.862

AC XY:

64166

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.898

AC:

37269

AN:

41516

American (AMR)

AF:

0.788

AC:

12054

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.843

AC:

2928

AN:

3472

East Asian (EAS)

AF:

0.804

AC:

4150

AN:

5160

South Asian (SAS)

AF:

0.834

AC:

4021

AN:

4822

European-Finnish (FIN)

AF:

0.860

AC:

9104

AN:

10592

Middle Eastern (MID)

AF:

0.904

AC:

264

AN:

292

European-Non Finnish (NFE)

AF:

0.876

AC:

59580

AN:

67988

Other (OTH)

AF:

0.848

AC:

1792

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

919

1838

2758

3677

4596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.868

Hom.:

10891

Bravo

AF:

0.862

Asia WGS

AF:

0.797

AC:

2771

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autosomal recessive limb-girdle muscular dystrophy type 2B (1)

Distal myopathy with anterior tibial onset (1)

Miyoshi muscular dystrophy 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

(source)

DANN

Benign

0.59

PhyloP100

-2.1

Mutation Taster

=17/83

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over