Variant 15-82851142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004839.4(HOMER2):c.843+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,570,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HOMER2
NM_004839.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0210

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-82851142-C-T is Benign according to our data. Variant chr15-82851142-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3057749.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4 linkuse as main transcript	c.843+9G>A		intron_variant		ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7 linkuse as main transcript	c.843+9G>A	intron_variant	1	NM_004839.4		Q9NSB8-2
HOMER2	ENST00000304231.12 linkuse as main transcript	c.876+9G>A	intron_variant	5		P1	Q9NSB8-1
HOMER2	ENST00000558552.1 linkuse as main transcript	n.723+9G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000556

AC:

AN:

197774

Hom.:

AF XY:

0.0000759

AC XY:

AN XY:

105414

show subpopulations

Gnomad AFR exome

AF:

0.0000833

Gnomad AMR exome

AF:

0.0000696

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000403

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000119

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1418044

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

702056

show subpopulations

Gnomad4 AFR exome

AF:

0.0000611

Gnomad4 AMR exome

AF:

0.0000253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000208

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.000221

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000329

Hom.:

Bravo

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HOMER2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

4.0

Dann

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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