2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A

Variant names:

• chr2-126693860-ACAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG-A
• NM_002101.5:c.107_190delAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTGCAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_002101.5(GYPC):​c.107_190delAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTGCAG variant causes a exon loss, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic,protective (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYPC NM_002101.5 exon_loss, splice_region
• Clinical Significance: Pathogenic; protective no assertion criteria provided P:1 B:1
• Conservation: PhyloP100: 3.35
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• 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 rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.107_190delAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTGCAG		exon_loss_variant, splice_region_variant	Exon 3 of 4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.107-3_187delCAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG	p.Glu36_Ile62del	splice_acceptor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	Exon 3 of 4	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.50-3_130delCAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG	p.Glu17_Ile43del	splice_acceptor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	Exon 2 of 3	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.44-3_124delCAGAGCCTGATCCAGGGATGTCTGGATGGCCGGATGGCAGAATGGAGACCTCCACCCCCACCATAATGGACATTGTCGTCATTG	p.Glu15_Ile41del	splice_acceptor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	Exon 4 of 5	1		ENSP00000349354.7

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

Jan 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Malaria, resistance to Benign:1

Jan 01, 2003

OMIM

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=106/94	disease causing (ClinVar)

Splicing

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

Other links and lift over

hg19: chr2-127451436;