chr2-71455820-C-G

Position:

• chr2-71455820-C-G

Variant summary

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

The ENST00000258104.8(DYSF):​c.88+1734C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,966 control chromosomes in the GnomAD database, including 10,663 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 0.37 (10663 hom., cov: 32)
• Consequence: DYSF ENST00000258104.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYSF	NM_003494.4	c.88+1734C>G		intron_variant		ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000258104.8	c.88+1734C>G		intron_variant		1	NM_003494.4	ENSP00000258104	A1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55707 AN: 151848 Hom.: 10661 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.367 AC: 55719 AN: 151966 Hom.: 10663 Cov.: 32 AF XY: 0.366 AC XY: 27215 AN XY: 74268

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.381

Alfa AF: 0.372 Hom.: 1382

Bravo AF: 0.374

Asia WGS AF: 0.376 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.75

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: rs4852259; hg19: chr2-71682950;