chr2-126696654-T-G

Position:

• chr2-126696654-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002101.5(GYPC):​c.*512T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 220,446 control chromosomes in the GnomAD database, including 8,457 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 0.28 (6643 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1814 hom.)
• Consequence: GYPC NM_002101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.*512T>G		3_prime_UTR_variant	4/4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.*512T>G		3_prime_UTR_variant	4/4	1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.*512T>G		3_prime_UTR_variant	5/5	1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.*512T>G		3_prime_UTR_variant	3/3	1		ENSP00000386904	A2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42431 AN: 152012 Hom.: 6630 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.208 AC: 14192 AN: 68316 Hom.: 1814 Cov.: 0 AF XY: 0.199 AC XY: 6957 AN XY: 34878

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.279 AC: 42489 AN: 152130 Hom.: 6643 Cov.: 32 AF XY: 0.280 AC XY: 20795 AN XY: 74362

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.280

Alfa AF: 0.226 Hom.: 8367

Bravo AF: 0.300

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs6568; hg19: chr2-127454230;