chr2-126690187-G-A

Variant names:

• chr2-126690187-G-A
• rs6709803
• NM_002101.5:c.50-68G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002101.5(GYPC):​c.50-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,147,440 control chromosomes in the GnomAD database, including 181,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27144 hom., cov: 33)
  • Exomes 𝑓: 0.55 (154520 hom.)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.34
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-126690187-G-A is Benign according to our data. Variant chr2-126690187-G-A is described in ClinVar as [Benign]. Clinvar id is 1257983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.50-68G>A		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.50-68G>A		intron_variant	Intron 1 of 3	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.50-3677G>A		intron_variant	Intron 1 of 2	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.-14-68G>A		intron_variant	Intron 2 of 4	1		ENSP00000349354.7

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90032 AN: 151960 Hom.: 27108 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.554 AC: 551251 AN: 995362 Hom.: 154520 AF XY: 0.548 AC XY: 282766 AN XY: 515610

African (AFR) AF: 0.706 AC: 17345 AN: 24562

American (AMR) AF: 0.489 AC: 21498 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 12690 AN: 23212

East Asian (EAS) AF: 0.605 AC: 22730 AN: 37568

South Asian (SAS) AF: 0.446 AC: 34314 AN: 76906

European-Finnish (FIN) AF: 0.551 AC: 29222 AN: 53078

Middle Eastern (MID) AF: 0.570 AC: 2724 AN: 4776

European-Non Finnish (NFE) AF: 0.561 AC: 385143 AN: 686126

Other (OTH) AF: 0.566 AC: 25585 AN: 45192

GnomAD4 genome AF: 0.593 AC: 90122 AN: 152078 Hom.: 27144 Cov.: 33 AF XY: 0.591 AC XY: 43942 AN XY: 74312

African (AFR) AF: 0.697 AC: 28933 AN: 41498

American (AMR) AF: 0.543 AC: 8297 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1862 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3374 AN: 5170

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4824

European-Finnish (FIN) AF: 0.559 AC: 5905 AN: 10558

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37631 AN: 67966

Other (OTH) AF: 0.604 AC: 1274 AN: 2110

Alfa AF: 0.592 Hom.: 4638

Bravo AF: 0.602

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.049
DANN	Benign	0.73
PhyloP100		-2.3
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: rs6709803; hg19: chr2-127447763; COSMIC: COSV52145028;