16-20314690-G-T

Variant names:

• chr16-20314690-G-T
• rs184827364
• NM_001502.4:c.1513C>A

Variant summary

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

The NM_001502.4(GP2):​c.1513C>A​(p.Pro505Thr) 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. 17/22 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. P505A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GP2 NM_001502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05539167).

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.1513C>A	p.Pro505Thr	missense	Exon 10 of 11	NP_001493.2	P55259-3
	GP2	NM_001007240.3		c.1522C>A	p.Pro508Thr	missense	Exon 11 of 12	NP_001007241.2	P55259-1
	GP2	NM_001007241.3		c.1081C>A	p.Pro361Thr	missense	Exon 10 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.1513C>A	p.Pro505Thr	missense	Exon 10 of 11	ENSP00000304044.6	P55259-3
	GP2	ENST00000381362.8	TSL:1	c.1522C>A	p.Pro508Thr	missense	Exon 11 of 12	ENSP00000370767.4	P55259-1
	GP2	ENST00000381360.9	TSL:1	c.1081C>A	p.Pro361Thr	missense	Exon 10 of 11	ENSP00000370765.5	P55259-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.099
DANN	Benign	0.13
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.52
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.11
Sift	Benign	0.62	T
Sift4G	Benign	0.98	T
Polyphen		0.15	B
Vest4		0.048
MutPred		0.28		Gain of catalytic residue at P508 (P = 0.0229)
MVP		0.37
MPC		0.17
ClinPred		0.033	T
GERP RS		-1.6
Varity_R		0.021
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs184827364; hg19: chr16-20326012;