chr16-20319726-C-A

Variant names:

• chr16-20319726-C-A
• rs201741257
• NM_001502.4:c.901G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001502.4(GP2):​c.901G>T​(p.Val301Phe) 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. 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. V301I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GP2 NM_001502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

GP2 (HGNC:4441): (glycoprotein 2) This gene encodes an integral membrane protein that is secreted from intracellular zymogen granules and associates with the plasma membrane via glycosylphosphatidylinositol (GPI) linkage. The encoded protein binds pathogens such as enterobacteria, thereby playing an important role in the innate immune response. The C-terminus of this protein is related to the C-terminus of the protein encoded by the neighboring gene, uromodulin (UMOD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP2	NM_001502.4	c.901G>T	p.Val301Phe	missense_variant	Exon 6 of 11	ENST00000302555.10	NP_001493.2
GP2	NM_001007240.3	c.910G>T	p.Val304Phe	missense_variant	Exon 7 of 12		NP_001007241.2
GP2	NM_001007241.3	c.469G>T	p.Val157Phe	missense_variant	Exon 6 of 11		NP_001007242.2
GP2	NM_001007242.3	c.460G>T	p.Val154Phe	missense_variant	Exon 5 of 10		NP_001007243.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP2	ENST00000302555.10	c.901G>T	p.Val301Phe	missense_variant	Exon 6 of 11	1	NM_001502.4	ENSP00000304044.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0072	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.2	.;.;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.96	D;P;P;.
Vest4		0.19
MutPred		0.65		.;.;Gain of sheet (P = 0.1208);.;
MVP		0.71
MPC		0.20
ClinPred		0.65	D
GERP RS		3.3
Varity_R		0.15
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -20

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

Publications

LitVar

Other links and lift over

dbSNP: rs201741257; hg19: chr16-20331048;