NM_001502.4:c.1285G>A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001502.4(GP2):​c.1285G>A​(p.Val429Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,613,740 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (19 hom., cov: 30)
  • Exomes 𝑓: 0.0050 (215 hom.)
• Consequence: GP2 NM_001502.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023725033).
• BP6: Variant 16-20317344-C-T is Benign according to our data. Variant chr16-20317344-C-T is described in ClinVar as [Benign]. Clinvar id is 1276754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP2	NM_001502.4	c.1285G>A	p.Val429Met	missense_variant	Exon 8 of 11	ENST00000302555.10	NP_001493.2
GP2	NM_001007240.3	c.1294G>A	p.Val432Met	missense_variant	Exon 9 of 12		NP_001007241.2
GP2	NM_001007241.3	c.853G>A	p.Val285Met	missense_variant	Exon 8 of 11		NP_001007242.2
GP2	NM_001007242.3	c.844G>A	p.Val282Met	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>A	p.Val429Met	missense_variant	Exon 8 of 11	1	NM_001502.4	ENSP00000304044.6
GP2	ENST00000381362.8	c.1294G>A	p.Val432Met	missense_variant	Exon 9 of 12	1		ENSP00000370767.4
GP2	ENST00000381360.9	c.853G>A	p.Val285Met	missense_variant	Exon 8 of 11	1		ENSP00000370765.5
GP2	ENST00000341642.9	c.844G>A	p.Val282Met	missense_variant	Exon 7 of 10	1		ENSP00000343861.5

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 738 AN: 152116 Hom.: 19 Cov.: 30

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0754

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.0111 AC: 2778 AN: 250928 Hom.: 85 AF XY: 0.0117 AC XY: 1588 AN XY: 135584

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0776

Gnomad SAS exome AF: 0.0346

Gnomad FIN exome AF: 0.00439

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00736

GnomAD4 exome AF: 0.00498 AC: 7272 AN: 1461506 Hom.: 215 Cov.: 31 AF XY: 0.00581 AC XY: 4222 AN XY: 727072

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0772

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.00462

Gnomad4 NFE exome AF: 0.000380

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00483 AC: 735 AN: 152234 Hom.: 19 Cov.: 30 AF XY: 0.00566 AC XY: 421 AN XY: 74438

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.0388

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00397 Hom.: 38

Bravo AF: 0.00425

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0117 AC: 1415

Asia WGS AF: 0.0640 AC: 222 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32581250) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;.;T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.86	D;D;D;D
MetaRNN	Benign	0.0024	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	.;.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.018	D;T;D;T
Sift4G	Benign	0.063	T;T;T;T
Polyphen		0.64	P;P;P;.
Vest4		0.19
MPC		0.51
ClinPred		0.022	T
GERP RS		1.3
Varity_R		0.080
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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;