Variant 5-139809526-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032289.4(PSD2):c.86G>A(p.Gly29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,240 control chromosomes in the GnomAD database, including 54 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 0.012 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 17 hom. )

Consequence

PSD2
NM_032289.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.382

Variant links:

Genes affected

PSD2 (HGNC:19092): (pleckstrin and Sec7 domain containing 2) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Predicted to be located in cleavage furrow and ruffle membrane. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

PSD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031118095).

BP6

Variant 5-139809526-G-A is Benign according to our data. Variant chr5-139809526-G-A is described in ClinVar as [Benign]. Clinvar id is 780566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1818/152354) while in subpopulation AFR AF= 0.0418 (1739/41590). AF 95% confidence interval is 0.0402. There are 37 homozygotes in gnomad4. There are 858 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PSD2	NM_032289.4 linkuse as main transcript	c.86G>A	p.Gly29Glu	missense_variant	2/15	ENST00000274710.4
PSD2	XM_017009976.2 linkuse as main transcript	c.86G>A	p.Gly29Glu	missense_variant	3/16
PSD2	XM_017009977.2 linkuse as main transcript	c.86G>A	p.Gly29Glu	missense_variant	3/16
PSD2	XM_047417829.1 linkuse as main transcript	c.86G>A	p.Gly29Glu	missense_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD2	ENST00000274710.4 linkuse as main transcript	c.86G>A	p.Gly29Glu	missense_variant	2/15	1	NM_032289.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1817

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00296

AC:

733

AN:

247932

Hom.:

AF XY:

0.00231

AC XY:

310

AN XY:

134358

show subpopulations

Gnomad AFR exome

AF:

0.0414

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00119

AC:

1732

AN:

1460886

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

762

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.0412

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.0119

AC:

1818

AN:

152354

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

858

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00303

Hom.:

Bravo

AF:

0.0134

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00369

AC:

448

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.031

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

REVEL

Benign

0.037

Sift

Benign

0.046

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.12

MVP

0.13

MPC

0.042

ClinPred

0.0063

GERP RS

-0.94

Varity_R

0.062

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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