2-126696654-T-G

Variant names:

• chr2-126696654-T-G
• rs6568
• NM_002101.5:c.*512T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

GYPC Gene-Disease associations (from GenCC):

• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	NM_002101.5	MANE Select	c.*512T>G		3_prime_UTR	Exon 4 of 4	NP_002092.1
	GYPC	NM_016815.4		c.*512T>G		3_prime_UTR	Exon 3 of 3	NP_058131.1
	GYPC	NM_001256584.2		c.*512T>G		3_prime_UTR	Exon 5 of 5	NP_001243513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	ENST00000259254.9	TSL:1 MANE Select	c.*512T>G		3_prime_UTR	Exon 4 of 4	ENSP00000259254.4
	GYPC	ENST00000409836.3	TSL:1	c.*512T>G		3_prime_UTR	Exon 3 of 3	ENSP00000386904.3
	GYPC	ENST00000356887.12	TSL:1	c.*512T>G		3_prime_UTR	Exon 5 of 5	ENSP00000349354.7

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

African (AFR) AF: 0.386 AC: 777 AN: 2014

American (AMR) AF: 0.297 AC: 1125 AN: 3792

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 239 AN: 1472

East Asian (EAS) AF: 0.377 AC: 1331 AN: 3534

South Asian (SAS) AF: 0.131 AC: 1202 AN: 9204

European-Finnish (FIN) AF: 0.177 AC: 521 AN: 2944

Middle Eastern (MID) AF: 0.0947 AC: 25 AN: 264

European-Non Finnish (NFE) AF: 0.198 AC: 8204 AN: 41354

Other (OTH) AF: 0.205 AC: 768 AN: 3738

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

African (AFR) AF: 0.404 AC: 16764 AN: 41496

American (AMR) AF: 0.301 AC: 4611 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2146 AN: 5158

South Asian (SAS) AF: 0.157 AC: 756 AN: 4824

European-Finnish (FIN) AF: 0.193 AC: 2045 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14705 AN: 67988

Other (OTH) AF: 0.280 AC: 591 AN: 2114

Alfa AF: 0.237 Hom.: 19346

Bravo AF: 0.300

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		1.4
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: rs6568; hg19: chr2-127454230;