2-126693860-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 variant, 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	UniProt
GYPC	NM_002101.5	c.107_190del	p.Glu36_Ala63del	splice_acceptor_variant, coding_sequence_variant, intron_variant	3/4	ENST00000259254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	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	P2
GYPC	ENST00000356887.12	c.44_127del	p.Glu15_Ala42del	splice_acceptor_variant, coding_sequence_variant, intron_variant	4/5	1		A2
GYPC	ENST00000409836.3	c.50_133del	p.Glu17_Ala44del	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/3	1		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;