2-126678893-G-T

Variant names:

• chr2-126678893-G-T
• rs13034269
• NM_002101.5:c.50-11362G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002101.5(GYPC):​c.50-11362G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,228 control chromosomes in the GnomAD database, including 436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (433 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	NM_002101.5	MANE Select	c.50-11362G>T		intron	N/A	NP_002092.1
	GYPC	NM_016815.4		c.50-14971G>T		intron	N/A	NP_058131.1
	GYPC	NM_001256584.2		c.-832-6935G>T		intron	N/A	NP_001243513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	ENST00000259254.9	TSL:1 MANE Select	c.50-11362G>T		intron	N/A	ENSP00000259254.4
	GYPC	ENST00000409836.3	TSL:1	c.50-14971G>T		intron	N/A	ENSP00000386904.3
	GYPC	ENST00000356887.12	TSL:1	c.-832-6935G>T		intron	N/A	ENSP00000349354.7

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11212 AN: 152018 Hom.: 434 Cov.: 33

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0862

GnomAD4 exome AF: 0.185 AC: 17 AN: 92 Hom.: 3 Cov.: 0 AF XY: 0.152 AC XY: 10 AN XY: 66

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.194 AC: 7 AN: 36

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.217 AC: 10 AN: 46

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.0737 AC: 11210 AN: 152136 Hom.: 433 Cov.: 33 AF XY: 0.0727 AC XY: 5410 AN XY: 74366

African (AFR) AF: 0.0703 AC: 2920 AN: 41514

American (AMR) AF: 0.0484 AC: 739 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5166

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4818

European-Finnish (FIN) AF: 0.0623 AC: 660 AN: 10600

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5827 AN: 67972

Other (OTH) AF: 0.0848 AC: 179 AN: 2110

Alfa AF: 0.0727 Hom.: 287

Bravo AF: 0.0712

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs13034269; hg19: chr2-127436469;