rs2696297

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000023.4(SGCA):​c.312+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 1,552,088 control chromosomes in the GnomAD database, including 544,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene SGCA is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.84 (53165 hom., cov: 32)
  • Exomes 𝑓: 0.84 (491445 hom.)
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2D

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

ENSG00000253730 (HGNC:):

ACMG classification

Specifications for SGCA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-50167819-C-T is Benign according to our data. Variant chr17-50167819-C-T is described in ClinVar as Benign. ClinVar VariationId is 669840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000023.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	NM_000023.4	MANE Select	c.312+83C>T		intron	N/A	NP_000014.1	A0A0S2Z4Q1
	SGCA	NM_001135697.3		c.312+83C>T		intron	N/A	NP_001129169.1	A0A0S2Z4P8
	SGCA	NR_135553.2		n.348+83C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000262018.8	TSL:1 MANE Select	c.312+83C>T		intron	N/A	ENSP00000262018.3	Q16586-1
	SGCA	ENST00000344627.10	TSL:1	c.312+83C>T		intron	N/A	ENSP00000345522.6	Q16586-2
	SGCA	ENST00000952408.1		c.402+83C>T		intron	N/A	ENSP00000622467.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127071 AN: 152060 Hom.: 53132 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.837 AC: 1172235 AN: 1399910 Hom.: 491445 Cov.: 23 AF XY: 0.838 AC XY: 585395 AN XY: 698652

African (AFR) AF: 0.821 AC: 26296 AN: 32036

American (AMR) AF: 0.781 AC: 34622 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 22038 AN: 25552

East Asian (EAS) AF: 0.955 AC: 37522 AN: 39298

South Asian (SAS) AF: 0.864 AC: 73443 AN: 85026

European-Finnish (FIN) AF: 0.840 AC: 44605 AN: 53116

Middle Eastern (MID) AF: 0.827 AC: 4654 AN: 5628

European-Non Finnish (NFE) AF: 0.833 AC: 879863 AN: 1056576

Other (OTH) AF: 0.843 AC: 49192 AN: 58330

GnomAD4 genome AF: 0.836 AC: 127163 AN: 152178 Hom.: 53165 Cov.: 32 AF XY: 0.836 AC XY: 62198 AN XY: 74384

African (AFR) AF: 0.827 AC: 34322 AN: 41514

American (AMR) AF: 0.805 AC: 12318 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2964 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4942 AN: 5172

South Asian (SAS) AF: 0.859 AC: 4142 AN: 4824

European-Finnish (FIN) AF: 0.849 AC: 8999 AN: 10598

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56692 AN: 67990

Other (OTH) AF: 0.860 AC: 1815 AN: 2110

Alfa AF: 0.834 Hom.: 58706

Bravo AF: 0.832

Asia WGS AF: 0.897 AC: 3118 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2D (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-0.61
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: rs2696297; hg19: chr17-48245180;