5-155890242-A-G

Variant names:

• chr5-155890242-A-G
• rs17617422
• ENST00000517913.5:c.-282+19818A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517913.5(SGCD):​c.-282+19818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,136 control chromosomes in the GnomAD database, including 3,637 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 0.19 (3637 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2F

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

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517913.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000517913.5	TSL:5	c.-282+19818A>G		intron	N/A	ENSP00000429378.1	Q92629-3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29015 AN: 152018 Hom.: 3629 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.191 AC: 29027 AN: 152136 Hom.: 3637 Cov.: 32 AF XY: 0.196 AC XY: 14539 AN XY: 74360

African (AFR) AF: 0.0827 AC: 3438 AN: 41556

American (AMR) AF: 0.416 AC: 6344 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1134 AN: 5148

South Asian (SAS) AF: 0.145 AC: 700 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2681 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13387 AN: 67988

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.178 Hom.: 1275

Bravo AF: 0.201

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17617422; hg19: chr5-155317252;