rs78193826

Variant names:

• chr16-20317344-C-G
• rs78193826
• NM_001502.4:c.1285G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-20317344-C-G
• chr16-20317344-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001502.4(GP2):​c.1285G>C​(p.Val429Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. V429M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GP2 NM_001502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1758253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP2	NM_001502.4	c.1285G>C	p.Val429Leu	missense_variant	Exon 8 of 11	ENST00000302555.10	NP_001493.2
GP2	NM_001007240.3	c.1294G>C	p.Val432Leu	missense_variant	Exon 9 of 12		NP_001007241.2
GP2	NM_001007241.3	c.853G>C	p.Val285Leu	missense_variant	Exon 8 of 11		NP_001007242.2
GP2	NM_001007242.3	c.844G>C	p.Val282Leu	missense_variant	Exon 7 of 10		NP_001007243.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP2	ENST00000302555.10	c.1285G>C	p.Val429Leu	missense_variant	Exon 8 of 11	1	NM_001502.4	ENSP00000304044.6
GP2	ENST00000381362.8	c.1294G>C	p.Val432Leu	missense_variant	Exon 9 of 12	1		ENSP00000370767.4
GP2	ENST00000381360.9	c.853G>C	p.Val285Leu	missense_variant	Exon 8 of 11	1		ENSP00000370765.5
GP2	ENST00000341642.9	c.844G>C	p.Val282Leu	missense_variant	Exon 7 of 10	1		ENSP00000343861.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250928 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135584

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461510 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Uncertain	0.44	.;.;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.4	.;.;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.26	T;D;T;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.65	P;P;D;.
Vest4		0.25
MutPred		0.58		.;.;Loss of sheet (P = 0.0817);.;
MVP		0.42
MPC		0.50
ClinPred		0.24	T
GERP RS		1.3
Varity_R		0.081
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs78193826; hg19: chr16-20328666;