chr13-93305563-G-A

Variant names:

• chr13-93305563-G-A
• rs2057525
• NM_005708.5:c.160+77947G>A

Variant summary

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

The NM_005708.5(GPC6):​c.160+77947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,954 control chromosomes in the GnomAD database, including 4,367 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 0.24 (4367 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 3 publications found

Genes affected

GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

GPC6 Gene-Disease associations (from GenCC):

• autosomal recessive omodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

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 (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+77947G>A		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+78881G>A		intron_variant	Intron 1 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.160+77947G>A		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35929 AN: 151836 Hom.: 4369 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.237 AC: 35950 AN: 151954 Hom.: 4367 Cov.: 32 AF XY: 0.237 AC XY: 17618 AN XY: 74270

African (AFR) AF: 0.277 AC: 11488 AN: 41416

American (AMR) AF: 0.263 AC: 4018 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1438 AN: 5140

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2255 AN: 10568

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14020 AN: 67954

Other (OTH) AF: 0.243 AC: 514 AN: 2116

Alfa AF: 0.220 Hom.: 6512

Bravo AF: 0.244

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		0.72
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: rs2057525; hg19: chr13-93957816;