chr2-71453502-T-C

Variant names:

• chr2-71453502-T-C
• rs6546693
• ENST00000685766.2:n.969A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000685766.2(ENSG00000289327):​n.969A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,110 control chromosomes in the GnomAD database, including 2,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2867 hom., cov: 32)
• Consequence: ENSG00000289327 ENST00000685766.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118

Genes affected

ENSG00000289327 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-71453502-T-C is Benign according to our data. Variant chr2-71453502-T-C is described in ClinVar as [Benign]. Clinvar id is 679856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYSF	NM_003494.4	c.-497T>C		upstream_gene_variant		ENST00000258104.8	NP_003485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYSF	ENST00000258104.8	c.-497T>C		upstream_gene_variant		1	NM_003494.4	ENSP00000258104.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24166 AN: 151992 Hom.: 2864 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.159 AC: 24196 AN: 152110 Hom.: 2867 Cov.: 32 AF XY: 0.163 AC XY: 12085 AN XY: 74368

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0767

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0991 Hom.: 1696

Bravo AF: 0.170

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.5
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6546693; hg19: chr2-71680632;