Variant 15-82849766-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004839.4(HOMER2):c.981C>T(p.Asp327=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,613,860 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 37 hom., cov: 33)

Exomes 𝑓: 0.026 ( 568 hom. )

Consequence

HOMER2
NM_004839.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.38

Variant links:

Genes affected

HOMER2 (HGNC:17513): (homer scaffold protein 2) This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The encoded protein is a postsynaptic density scaffolding protein. Alternative splicing results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 14. [provided by RefSeq, Jun 2011]

HOMER2 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=-0.78).

BP6

Variant 15-82849766-G-A is Benign according to our data. Variant chr15-82849766-G-A is described in ClinVar as [Benign]. Clinvar id is 508610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0177 (2693/152224) while in subpopulation SAS AF= 0.0272 (131/4820). AF 95% confidence interval is 0.0257. There are 37 homozygotes in gnomad4. There are 1321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2693 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4 linkuse as main transcript	c.981C>T	p.Asp327=	synonymous_variant	9/9	ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7 linkuse as main transcript	c.981C>T	p.Asp327=	synonymous_variant	9/9	1	NM_004839.4		Q9NSB8-2
HOMER2	ENST00000304231.12 linkuse as main transcript	c.1014C>T	p.Asp338=	synonymous_variant	9/9	5		P1	Q9NSB8-1
HOMER2	ENST00000558552.1 linkuse as main transcript	n.861C>T		non_coding_transcript_exon_variant	3/3	2
HOMER2	ENST00000558090.2 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2692

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0197

AC:

4913

AN:

249088

Hom.:

AF XY:

0.0212

AC XY:

2862

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.00841

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00122

Gnomad SAS exome

AF:

0.0272

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0260

Gnomad OTH exome

AF:

0.0179

GnomAD4 exome

AF:

0.0257

AC:

37547

AN:

1461636

Hom.:

568

Cov.:

AF XY:

0.0262

AC XY:

19019

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00409

Gnomad4 AMR exome

AF:

0.00868

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.00113

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0285

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0177

AC:

2693

AN:

152224

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1321

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0238

Gnomad4 NFE

AF:

0.0267

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0224

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0254

EpiControl

AF:

0.0246

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 20, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

DANN

Benign

0.86

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

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