rs2696297

Variant names:

• chr17-50167819-C-A
• rs2696297
• NM_000023.4:c.312+83C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50167819-C-A
• chr17-50167819-C-G
• chr17-50167819-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000023.4(SGCA):​c.312+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• Publications: 14 publications found

Genes affected

SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SGCA Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, Orphanet

ENSG00000253730 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCA	NM_000023.4	c.312+83C>A		intron_variant	Intron 3 of 9	ENST00000262018.8	NP_000014.1
SGCA	NM_001135697.3	c.312+83C>A		intron_variant	Intron 3 of 7		NP_001129169.1
SGCA	NR_135553.2	n.348+83C>A		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.312+83C>A		intron_variant	Intron 3 of 9	1	NM_000023.4	ENSP00000262018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1401002 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 699172

African (AFR) AF: 0.00 AC: 0 AN: 32066

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25568

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.00 AC: 0 AN: 85052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057538

Other (OTH) AF: 0.00 AC: 0 AN: 58354

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 58706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.43
PhyloP100		-0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2696297; hg19: chr17-48245180;