15-82854635-C-T

Position:

• chr15-82854635-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004839.4(HOMER2):​c.651+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,608,334 control chromosomes in the GnomAD database, including 6,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (839 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5653 hom.)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.130

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-82854635-C-T is Benign according to our data. Variant chr15-82854635-C-T is described in ClinVar as [Benign]. Clinvar id is 508119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.651+9G>A		intron_variant		ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.651+9G>A		intron_variant		1	NM_004839.4	ENSP00000407634
HOMER2	ENST00000304231.12	c.684+9G>A		intron_variant		5		ENSP00000305632	P1
HOMER2	ENST00000558817.1	c.408+9G>A		intron_variant		3		ENSP00000454125

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14791 AN: 152056 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.0964

GnomAD3 exomes AF: 0.0952 AC: 23215 AN: 243976 Hom.: 1425 AF XY: 0.0887 AC XY: 11754 AN XY: 132466

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.0805

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.0457

Gnomad FIN exome AF: 0.0659

Gnomad NFE exome AF: 0.0704

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.0813 AC: 118336 AN: 1456160 Hom.: 5653 Cov.: 33 AF XY: 0.0799 AC XY: 57849 AN XY: 723798

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.0453

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.0741

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.0974 AC: 14817 AN: 152174 Hom.: 839 Cov.: 32 AF XY: 0.0980 AC XY: 7288 AN XY: 74384

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0726

Gnomad4 OTH AF: 0.0958

Alfa AF: 0.0802 Hom.: 643

Bravo AF: 0.104

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 11, 2018	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs2306428; hg19: chr15-83523387;