2-126690265-G-A

Variant names:

• chr2-126690265-G-A
• rs56070638
• NM_002101.5:c.60G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002101.5(GYPC):​c.60G>A​(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,611,996 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (19 hom.)
• Consequence: GYPC NM_002101.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-126690265-G-A is Benign according to our data. Variant chr2-126690265-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BS2: High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 2 of 4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 2 of 4	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000356887.12	c.-4G>A		5_prime_UTR_variant	Exon 3 of 5	1		ENSP00000349354.7
GYPC	ENST00000409836.3	c.50-3599G>A		intron_variant	Intron 1 of 2	1		ENSP00000386904.3

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 505 AN: 152108 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00395

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00313 AC: 786 AN: 251394 AF XY: 0.00311

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0135

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00289 AC: 4226 AN: 1459770 Hom.: 19 Cov.: 30 AF XY: 0.00277 AC XY: 2015 AN XY: 726322

African (AFR) AF: 0.000658 AC: 22 AN: 33432

American (AMR) AF: 0.00168 AC: 75 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000557 AC: 48 AN: 86204

European-Finnish (FIN) AF: 0.0137 AC: 732 AN: 53408

Middle Eastern (MID) AF: 0.000871 AC: 5 AN: 5740

European-Non Finnish (NFE) AF: 0.00289 AC: 3209 AN: 1110134

Other (OTH) AF: 0.00206 AC: 124 AN: 60328

GnomAD4 genome AF: 0.00332 AC: 505 AN: 152226 Hom.: 4 Cov.: 32 AF XY: 0.00368 AC XY: 274 AN XY: 74438

African (AFR) AF: 0.000867 AC: 36 AN: 41542

American (AMR) AF: 0.00307 AC: 47 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00396 AC: 269 AN: 68010

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00265 Hom.: 1

Bravo AF: 0.00209

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GYPC: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.88
DANN	Benign	0.31
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56070638; hg19: chr2-127447841; COSMIC: COSV99392152;