rs9677779

chr2-71675906-G-A

Variant summary

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

The NM_001130987.2(DYSF):c.5884+1610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,852 control chromosomes in the GnomAD database, including 2,665 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 0.18 (2665 hom., cov: 32)
• Consequence: DYSF NM_001130987.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYSF	NM_001130987.2	c.5884+1610G>A		intron_variant		ENST00000410020.8
DYSF	NM_003494.4	c.5767+1610G>A		intron_variant		ENST00000258104.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYSF	ENST00000258104.8	c.5767+1610G>A		intron_variant		1	NM_003494.4	A1
DYSF	ENST00000410020.8	c.5884+1610G>A		intron_variant		1	NM_001130987.2	A1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27502 AN: 151744 Hom.: 2663 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.181 AC: 27519 AN: 151852 Hom.: 2665 Cov.: 32 AF XY: 0.182 AC XY: 13493 AN XY: 74194

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.176

Alfa AF: 0.328 Hom.: 9972

Bravo AF: 0.169

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.62

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: rs9677779; hg19: chr2-71903036;