rs9677779

Variant names:

• chr2-71675906-G-A
• rs9677779
• NM_001130987.2:c.5884+1610G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DYSF	NM_001130987.2	c.5884+1610G>A		intron_variant	Intron 52 of 55	ENST00000410020.8	NP_001124459.1
DYSF	NM_003494.4	c.5767+1610G>A		intron_variant	Intron 51 of 54	ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000410020.8	c.5884+1610G>A		intron_variant	Intron 52 of 55	1	NM_001130987.2	ENSP00000386881.3
DYSF	ENST00000258104.8	c.5767+1610G>A		intron_variant	Intron 51 of 54	1	NM_003494.4	ENSP00000258104.3

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

African (AFR) AF: 0.159 AC: 6593 AN: 41392

American (AMR) AF: 0.123 AC: 1870 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3466

East Asian (EAS) AF: 0.0748 AC: 387 AN: 5172

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4806

European-Finnish (FIN) AF: 0.234 AC: 2459 AN: 10518

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14061 AN: 67924

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.449 Hom.: 24645

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
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9677779; hg19: chr2-71903036;