chr2-126690251-ACAGAGCCTGATCCGGGGATGGCCTCTGCCTCCACCACAATGCATACTACCACCATTG-A

Position:

• chr2-126690251-ACAGAGCCTGATCCGGGGATGGCCTCTGCCTCCACCACAATGCATACTACCACCATTG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_002101.5(GYPC):​c.50_106del​(p.Ala23_Met41del) variant causes a splice acceptor, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYPC NM_002101.5 splice_acceptor, coding_sequence, intron
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 2.50

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.14470284 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.50_106del	p.Ala23_Met41del	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.50_106del	p.Ala23_Met41del	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/4	1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.-14_43del		splice_acceptor_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant	3/5	1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.50-3609_50-3553del		intron_variant		1		ENSP00000386904	A2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Blood group, Gerbich system Other:1

Affects, no assertion criteria provided

literature only

OMIM

Feb 01, 1991

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-127447827;