chr2-126695685-A-C

Position:

• chr2-126695685-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002101.5(GYPC):​c.191-261A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,136 control chromosomes in the GnomAD database, including 5,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5036 hom., cov: 34)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.437

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-126695685-A-C is Benign according to our data. Variant chr2-126695685-A-C is described in ClinVar as [Benign]. Clinvar id is 1262546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.191-261A>C		intron_variant		ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.191-261A>C		intron_variant		1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.128-261A>C		intron_variant		1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.134-261A>C		intron_variant		1		ENSP00000386904	A2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37843 AN: 152018 Hom.: 5028 Cov.: 34

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.249 AC: 37871 AN: 152136 Hom.: 5036 Cov.: 34 AF XY: 0.251 AC XY: 18628 AN XY: 74362

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.256

Alfa AF: 0.118 Hom.: 191

Bravo AF: 0.264

Asia WGS AF: 0.248 AC: 858 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1530147; hg19: chr2-127453261;