rs56988800

chr2-71460988-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003494.4(DYSF):c.88+6902C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 151,256 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.026 (85 hom., cov: 31)
• Consequence: DYSF NM_003494.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYSF	NM_003494.4	c.88+6902C>A		intron_variant		ENST00000258104.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYSF	ENST00000258104.8	c.88+6902C>A		intron_variant		1	NM_003494.4	A1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3897 AN: 151138 Hom.: 84 Cov.: 31

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0243

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0258 AC: 3905 AN: 151256 Hom.: 85 Cov.: 31 AF XY: 0.0258 AC XY: 1906 AN XY: 73852

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0230

Alfa AF: 0.0215 Hom.: 7

Bravo AF: 0.0273

Asia WGS AF: 0.0160 AC: 54 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
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

Other links and lift over

dbSNP: rs56988800; hg19: chr2-71688118;