chr2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A

Position:

• chr2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_002101.5(GYPC):​c.107_190del​(p.Glu36_Ala63del) 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 Pathogenic,protective (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYPC NM_002101.5 splice_acceptor, coding_sequence, intron
• Clinical Significance: Pathogenic; protective no assertion criteria provided P:1 B:1
• Conservation: PhyloP100: 3.35

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 7 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.21447028 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A is Pathogenic according to our data. Variant chr2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A is described in ClinVar as [Pathogenic, protective]. Clinvar id is 17725.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.107_190del	p.Glu36_Ala63del	splice_acceptor_variant, coding_sequence_variant, intron_variant	3/4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.107_190del	p.Glu36_Ala63del	splice_acceptor_variant, coding_sequence_variant, intron_variant	3/4	1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.44_127del	p.Glu15_Ala42del	splice_acceptor_variant, coding_sequence_variant, intron_variant	4/5	1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.50_133del	p.Glu17_Ala44del	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/3	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: Pathogenic; protective

Submissions summary: Pathogenic:1 Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Glycophorin c, gerbich variant Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2003

- -

Malaria, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jan 01, 2003

- -

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: chr2-127451436;