16-20311280-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001502.4(GP2):c.1548G>T(p.Gly516Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,596,846 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 16 hom. )

Consequence

GP2
NM_001502.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00001378

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.436

Variant links:

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]

GP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 16-20311280-C-A is Benign according to our data. Variant chr16-20311280-C-A is described in ClinVar as [Benign]. Clinvar id is 786288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.436 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00808 (1231/152292) while in subpopulation AFR AF= 0.0273 (1133/41562). AF 95% confidence interval is 0.0259. There are 19 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP2	NM_001502.4 link	c.1548G>T	p.Gly516Gly	splice_region_variant, synonymous_variant	Exon 11 of 11	ENST00000302555.10	NP_001493.2	P55259-3Q68D34B7Z1G2
GP2	NM_001007240.3 link	c.1557G>T	p.Gly519Gly	splice_region_variant, synonymous_variant	Exon 12 of 12		NP_001007241.2	P55259-1B7Z1G2
GP2	NM_001007241.3 link	c.1116G>T	p.Gly372Gly	splice_region_variant, synonymous_variant	Exon 11 of 11		NP_001007242.2	B7Z1G2
GP2	NM_001007242.3 link	c.1107G>T	p.Gly369Gly	splice_region_variant, synonymous_variant	Exon 10 of 10		NP_001007243.2	B7Z1G2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GP2	ENST00000302555.10 link	c.1548G>T	p.Gly516Gly	splice_region_variant, synonymous_variant	Exon 11 of 11	1	NM_001502.4	ENSP00000304044.6	P55259-3
GP2	ENST00000381362.8 link	c.1557G>T	p.Gly519Gly	splice_region_variant, synonymous_variant	Exon 12 of 12	1		ENSP00000370767.4	P55259-1
GP2	ENST00000381360.9 link	c.1116G>T	p.Gly372Gly	splice_region_variant, synonymous_variant	Exon 11 of 11	1		ENSP00000370765.5	P55259-2
GP2	ENST00000341642.9 link	c.1107G>T	p.Gly369Gly	splice_region_variant, synonymous_variant	Exon 10 of 10	1		ENSP00000343861.5	P55259-4

Frequencies

GnomAD3 genomes

AF:

0.00810

AC:

1232

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00244

AC:

613

AN:

251040

Hom.:

AF XY:

0.00192

AC XY:

261

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000894

AC:

1291

AN:

1444554

Hom.:

Cov.:

AF XY:

0.000826

AC XY:

595

AN XY:

720012

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000931

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00808

AC:

1231

AN:

152292

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00962

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.0

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over