rs2569031

Variant names:

• chr5-155817661-T-C
• rs2569031
• ENST00000755060.1:n.472-4392T>C

Variant summary

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

The ENST00000755060.1(ENSG00000298352):​n.472-4392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,846 control chromosomes in the GnomAD database, including 16,955 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 0.47 (16955 hom., cov: 31)
• Consequence: ENSG00000298352 ENST00000755060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 0 publications found

Genes affected

ENSG00000298352 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-208+88671T>C		intron_variant	Intron 1 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-344-52683T>C		intron_variant	Intron 1 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-288-52683T>C		intron_variant	Intron 1 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.-165+88671T>C		intron_variant	Intron 1 of 8		XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000298352	ENST00000755060.1	n.472-4392T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70973 AN: 151728 Hom.: 16930 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.468 AC: 71044 AN: 151846 Hom.: 16955 Cov.: 31 AF XY: 0.470 AC XY: 34871 AN XY: 74192

African (AFR) AF: 0.455 AC: 18816 AN: 41378

American (AMR) AF: 0.635 AC: 9687 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1946 AN: 5170

South Asian (SAS) AF: 0.437 AC: 2101 AN: 4804

European-Finnish (FIN) AF: 0.444 AC: 4670 AN: 10514

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30717 AN: 67954

Other (OTH) AF: 0.485 AC: 1019 AN: 2102

Alfa AF: 0.445 Hom.: 1922

Bravo AF: 0.482

Asia WGS AF: 0.411 AC: 1431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.50
PhyloP100		0.48

Splicing

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

Other links and lift over

dbSNP: rs2569031; hg19: chr5-155244671;