2-126662652-A-G

Variant names:

• chr2-126662652-A-G
• rs10928979
• NM_002101.5:c.49+6340A>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.49+6340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,020 control chromosomes in the GnomAD database, including 21,508 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 0.51 (21508 hom., cov: 32)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.49+6340A>G		intron_variant	Intron 1 of 3	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.49+6340A>G		intron_variant	Intron 1 of 3	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.49+6340A>G		intron_variant	Intron 1 of 2	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.-833+6340A>G		intron_variant	Intron 1 of 4	1		ENSP00000349354.7
GYPC	ENST00000459787.1	n.171+6340A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77860 AN: 151902 Hom.: 21508 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.512 AC: 77887 AN: 152020 Hom.: 21508 Cov.: 32 AF XY: 0.518 AC XY: 38454 AN XY: 74300

African (AFR) AF: 0.283 AC: 11736 AN: 41450

American (AMR) AF: 0.552 AC: 8428 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3349 AN: 5156

South Asian (SAS) AF: 0.537 AC: 2583 AN: 4812

European-Finnish (FIN) AF: 0.649 AC: 6864 AN: 10574

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40975 AN: 67962

Other (OTH) AF: 0.532 AC: 1123 AN: 2110

Alfa AF: 0.557 Hom.: 36465

Bravo AF: 0.494

Asia WGS AF: 0.538 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.75
DANN	Benign	0.44
PhyloP100		-1.1
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: rs10928979; hg19: chr2-127420228;