rs187204080

Variant names:

• chr5-156757775-G-A
• rs187204080
• NM_000337.6:c.699+71G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000337.6(SGCD):​c.699+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,547,220 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.247
• Publications: 3 publications found

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD 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 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-156757775-G-A is Benign according to our data. Variant chr5-156757775-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 48124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00231 (352/152320) while in subpopulation AFR AF = 0.00818 (340/41574). AF 95% confidence interval is 0.00746. There are 2 homozygotes in GnomAd4. There are 152 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.699+71G>A		intron_variant	Intron 8 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.699+71G>A		intron_variant	Intron 8 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.696+71G>A		intron_variant	Intron 7 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.770G>A	p.Ter257Ter	stop_retained_variant	Exon 10 of 10	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 351 AN: 152202 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000468 AC: 79 AN: 168822 AF XY: 0.000312

Gnomad AFR exome AF: 0.00785

Gnomad AMR exome AF: 0.0000433

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000217 AC: 303 AN: 1394900 Hom.: 1 Cov.: 31 AF XY: 0.000182 AC XY: 125 AN XY: 687764

African (AFR) AF: 0.00843 AC: 268 AN: 31806

American (AMR) AF: 0.000225 AC: 8 AN: 35528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24498

East Asian (EAS) AF: 0.00 AC: 0 AN: 37046

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 76042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50204

Middle Eastern (MID) AF: 0.000194 AC: 1 AN: 5142

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076840

Other (OTH) AF: 0.000415 AC: 24 AN: 57794

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152320 Hom.: 2 Cov.: 32 AF XY: 0.00204 AC XY: 152 AN XY: 74478

African (AFR) AF: 0.00818 AC: 340 AN: 41574

American (AMR) AF: 0.000392 AC: 6 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00270

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Nov 13, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 15, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

X257X in exon 8 of SGCD: This variant is not expected to have clinical significa nce because it does not alter the stop codon and is not located near a splice ju nction. This variant was present in 3.0% (10/334) of African American control ch romosomes (LMM unpublished data) and in 0.9% (33/3832) of African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS/; dbSNP rs187204080). -

Jan 24, 2014

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. -

Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L Benign:1

Aug 10, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Sep 26, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1L Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.71
DANN	Benign	0.55
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

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: rs187204080; hg19: chr5-156184786;