15-82849950-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004839.4(HOMER2):c.844-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,582,130 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (120 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (96 hom.)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.390

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-82849950-G-A is Benign according to our data. Variant chr15-82849950-G-A is described in ClinVar as [Benign]. Clinvar id is 683266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4	c.844-47C>T		intron_variant		ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7	c.844-47C>T		intron_variant		1	NM_004839.4
HOMER2	ENST00000304231.12	c.877-47C>T		intron_variant		5		P1
HOMER2	ENST00000558552.1	n.724-47C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3269 AN: 152172 Hom.: 121 Cov.: 33

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00850

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00711 AC: 1689 AN: 237626 Hom.: 47 AF XY: 0.00573 AC XY: 737 AN XY: 128616

Gnomad AFR exome AF: 0.0731

Gnomad AMR exome AF: 0.00482

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.000225

Gnomad SAS exome AF: 0.000215

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00561

GnomAD4 exome AF: 0.00331 AC: 4730 AN: 1429840 Hom.: 96 Cov.: 25 AF XY: 0.00298 AC XY: 2120 AN XY: 710644

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.00539

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000931

Gnomad4 OTH exome AF: 0.00787

GnomAD4 genome AF: 0.0215 AC: 3279 AN: 152290 Hom.: 120 Cov.: 33 AF XY: 0.0208 AC XY: 1550 AN XY: 74452

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.00849

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.0153 Hom.: 12

Bravo AF: 0.0244

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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	-0.79
Cadd	Benign	2.2
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: rs7164147; hg19: chr15-83518702;