rs84182

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.13
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]

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=-0.89).
BP6
Variant 2-71644106-A-G is Benign according to our data. Variant chr2-71644106-A-G is described in ClinVar as [Benign]. Clinvar id is 259080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71644106-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DYSFNM_001130987.2 linkuse as main transcriptc.4626+43A>G intron_variant ENST00000410020.8
DYSFNM_003494.4 linkuse as main transcriptc.4509+43A>G intron_variant ENST00000258104.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DYSFENST00000258104.8 linkuse as main transcriptc.4509+43A>G intron_variant 1 NM_003494.4 A1O75923-1
DYSFENST00000410020.8 linkuse as main transcriptc.4626+43A>G intron_variant 1 NM_001130987.2 A1O75923-13

Frequencies

GnomAD3 genomes
AF:
0.867
AC:
131840
AN:
152038
Hom.:
57324
Cov.:
31
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
GnomAD3 exomes
AF:
0.845
AC:
170153
AN:
201330
Hom.:
72285
AF XY:
0.850
AC XY:
91206
AN XY:
107296
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 SAS exome
AF:
0.846
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.:
20
AF XY:
0.871
AC XY:
585829
AN XY:
672776
show subpopulations
Gnomad4 AFR exome
AF:
0.898
Gnomad4 AMR exome
AF:
0.720
Gnomad4 ASJ exome
AF:
0.858
Gnomad4 EAS exome
AF:
0.788
Gnomad4 SAS exome
AF:
0.848
Gnomad4 FIN exome
AF:
0.857
Gnomad4 NFE exome
AF:
0.882
Gnomad4 OTH exome
AF:
0.865
GnomAD4 genome
AF:
0.867
AC:
131925
AN:
152156
Hom.:
57360
Cov.:
31
AF XY:
0.862
AC XY:
64166
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.898
Gnomad4 AMR
AF:
0.788
Gnomad4 ASJ
AF:
0.843
Gnomad4 EAS
AF:
0.804
Gnomad4 SAS
AF:
0.834
Gnomad4 FIN
AF:
0.860
Gnomad4 NFE
AF:
0.876
Gnomad4 OTH
AF:
0.848
Alfa
AF:
0.867
Hom.:
10572
Bravo
AF:
0.862
Asia WGS
AF:
0.797
AC:
2771
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Distal myopathy with anterior tibial onset Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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. -
Autosomal recessive limb-girdle muscular dystrophy type 2B Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
Miyoshi muscular dystrophy 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJun 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.13
DANN
Benign
0.59

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.

Other links and lift over

dbSNP: rs84182; hg19: chr2-71871236; API