chr2-71481990-G-A

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.239+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,601,178 control chromosomes in the GnomAD database, including 6,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 733 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5924 hom. )

Consequence

DYSF
NM_001130987.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0680

Publications

1 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=-0.9).

BP6

Variant 2-71481990-G-A is Benign according to our data. Variant chr2-71481990-G-A is described in ClinVar as Benign. ClinVar VariationId is 94288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 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.239+20G>A	intron	N/A	NP_001124459.1	O75923-13
DYSF	NM_003494.4	MANE Plus Clinical	c.236+20G>A	intron	N/A	NP_003485.1	O75923-1
DYSF	NM_001130981.2		c.236+20G>A	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.239+20G>A	intron	N/A	ENSP00000386881.3	O75923-13
DYSF	ENST00000258104.8	TSL:1 MANE Plus Clinical	c.236+20G>A	intron	N/A	ENSP00000258104.3	O75923-1
DYSF	ENST00000409582.7	TSL:1	c.236+20G>A	intron	N/A	ENSP00000386547.3	O75923-7

Frequencies

GnomAD3 genomes

AF:

0.0899

AC:

13678

AN:

152102

Hom.:

734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.0862

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0733

Gnomad OTH

AF:

0.0883

GnomAD2 exomes

AF:

0.0974

AC:

24269

AN:

249230

AF XY:

0.0911

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0753

Gnomad OTH exome

AF:

0.0850

GnomAD4 exome

AF:

0.0797

AC:

115446

AN:

1448958

Hom.:

5924

Cov.:

AF XY:

0.0788

AC XY:

56824

AN XY:

721570

show subpopulations

African (AFR)

AF:

0.122

AC:

4037

AN:

33180

American (AMR)

AF:

0.265

AC:

11787

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

1202

AN:

25996

East Asian (EAS)

AF:

0.0158

AC:

628

AN:

39622

South Asian (SAS)

AF:

0.0929

AC:

7971

AN:

85788

European-Finnish (FIN)

AF:

0.0361

AC:

1927

AN:

53372

Middle Eastern (MID)

AF:

0.0770

AC:

418

AN:

5432

European-Non Finnish (NFE)

AF:

0.0751

AC:

82653

AN:

1101114

Other (OTH)

AF:

0.0805

AC:

4823

AN:

59942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

5047

10093

15140

20186

25233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3216

6432

9648

12864

16080

<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:

0.0900

AC:

13695

AN:

152220

Hom.:

733

Cov.:

AF XY:

0.0886

AC XY:

6594

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.115

AC:

4796

AN:

41526

American (AMR)

AF:

0.174

AC:

2653

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.0157

AC:

AN:

5168

South Asian (SAS)

AF:

0.0867

AC:

418

AN:

4822

European-Finnish (FIN)

AF:

0.0308

AC:

327

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0733

AC:

4983

AN:

68002

Other (OTH)

AF:

0.0874

AC:

185

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

628

1256

1883

2511

3139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0812

Hom.:

368

Bravo

AF:

0.106

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Miyoshi muscular dystrophy 1 (1)

Neuromuscular disease caused by qualitative or quantitative defects of dysferlin (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.51

PhyloP100

-0.068

Mutation Taster

=100/0

polymorphism (auto)

(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

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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