16-20318269-C-T

Variant names:

• chr16-20318269-C-T
• rs145287300
• NM_001502.4:c.1169G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001502.4(GP2):​c.1169G>A​(p.Arg390Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,612,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R390W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: GP2 NM_001502.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.510
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04690537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001502.4. 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
	GP2	NM_001502.4	MANE Select	c.1169G>A	p.Arg390Gln	missense	Exon 7 of 11	NP_001493.2	P55259-3
	GP2	NM_001007240.3		c.1178G>A	p.Arg393Gln	missense	Exon 8 of 12	NP_001007241.2	P55259-1
	GP2	NM_001007241.3		c.737G>A	p.Arg246Gln	missense	Exon 7 of 11	NP_001007242.2	P55259-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP2	ENST00000302555.10	TSL:1 MANE Select	c.1169G>A	p.Arg390Gln	missense	Exon 7 of 11	ENSP00000304044.6	P55259-3
	GP2	ENST00000381362.8	TSL:1	c.1178G>A	p.Arg393Gln	missense	Exon 8 of 12	ENSP00000370767.4	P55259-1
	GP2	ENST00000381360.9	TSL:1	c.737G>A	p.Arg246Gln	missense	Exon 7 of 11	ENSP00000370765.5	P55259-2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000875 AC: 22 AN: 251354 AF XY: 0.0000663

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1460570 Hom.: 0 Cov.: 30 AF XY: 0.0000633 AC XY: 46 AN XY: 726670

African (AFR) AF: 0.000419 AC: 14 AN: 33442

American (AMR) AF: 0.000313 AC: 14 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1110824

Other (OTH) AF: 0.0000166 AC: 1 AN: 60338

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74332

African (AFR) AF: 0.000410 AC: 17 AN: 41440

American (AMR) AF: 0.000262 AC: 4 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.000178

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.68	N
PhyloP100		0.51
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.10
Sift	Benign	0.56	T
Sift4G	Benign	0.34	T
Polyphen		0.14	B
Vest4		0.15
MutPred		0.63		Loss of sheet (P = 0.1398)
MVP		0.22
MPC		0.17
ClinPred		0.0092	T
GERP RS		-0.16
Varity_R		0.027
gMVP		0.30
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: rs145287300; hg19: chr16-20329591; COSMIC: COSV100221435; COSMIC: COSV100221435;