2-126690187-G-A

Position:

• chr2-126690187-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002101.5(GYPC):​c.50-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,147,440 control chromosomes in the GnomAD database, including 181,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27144 hom., cov: 33)
  • Exomes 𝑓: 0.55 (154520 hom.)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.34

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-126690187-G-A is Benign according to our data. Variant chr2-126690187-G-A is described in ClinVar as [Benign]. Clinvar id is 1257983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.50-68G>A		intron_variant		ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.50-68G>A		intron_variant		1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.-14-68G>A		intron_variant		1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.50-3677G>A		intron_variant		1		ENSP00000386904	A2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90032 AN: 151960 Hom.: 27108 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.554 AC: 551251 AN: 995362 Hom.: 154520 AF XY: 0.548 AC XY: 282766 AN XY: 515610

Gnomad4 AFR exome AF: 0.706

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.593 AC: 90122 AN: 152078 Hom.: 27144 Cov.: 33 AF XY: 0.591 AC XY: 43942 AN XY: 74312

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.604

Alfa AF: 0.431 Hom.: 1148

Bravo AF: 0.602

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.049
DANN	Benign	0.73

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: rs6709803; hg19: chr2-127447763; COSMIC: COSV52145028;