2-126693911-T-G

Variant names:

• chr2-126693911-T-G
• rs753718670
• NM_002101.5:c.154T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002101.5(GYPC):​c.154T>G​(p.Ser52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S52P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYPC NM_002101.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046707064).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	NM_002101.5	MANE Select	c.154T>G	p.Ser52Ala	missense	Exon 3 of 4	NP_002092.1	P04921-1
	GYPC	NM_016815.4		c.97T>G	p.Ser33Ala	missense	Exon 2 of 3	NP_058131.1	P04921-3
	GYPC	NM_001256584.2		c.91T>G	p.Ser31Ala	missense	Exon 4 of 5	NP_001243513.1	P04921-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPC	ENST00000259254.9	TSL:1 MANE Select	c.154T>G	p.Ser52Ala	missense	Exon 3 of 4	ENSP00000259254.4	P04921-1
	GYPC	ENST00000409836.3	TSL:1	c.97T>G	p.Ser33Ala	missense	Exon 2 of 3	ENSP00000386904.3	P04921-3
	GYPC	ENST00000356887.12	TSL:1	c.91T>G	p.Ser31Ala	missense	Exon 4 of 5	ENSP00000349354.7	P04921-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.31
DANN	Benign	0.38
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.80
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.016
Sift	Benign	0.35	T
Sift4G	Benign	0.87	T
Polyphen		0.033	B
Vest4		0.20
MutPred		0.21		Loss of glycosylation at S52 (P = 0.012)
MVP		0.030
MPC		0.0055
ClinPred		0.045	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.039
Mutation Taster		=96/4	polymorphism

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: rs753718670; hg19: chr2-127451487;