rs1010820

Variant names:

• chr15-82946202-T-A
• rs1010820
• NM_004839.4:c.5+6329A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004839.4(HOMER2):​c.5+6329A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,164 control chromosomes in the GnomAD database, including 3,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3027 hom., cov: 32)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 68

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259805 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.5+6329A>T		intron_variant	Intron 1 of 8	ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.5+6329A>T		intron_variant	Intron 1 of 8	1	NM_004839.4	ENSP00000407634.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29365 AN: 152046 Hom.: 3026 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29387 AN: 152164 Hom.: 3027 Cov.: 32 AF XY: 0.187 AC XY: 13906 AN XY: 74378

African (AFR) AF: 0.174 AC: 7224 AN: 41492

American (AMR) AF: 0.214 AC: 3273 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.115 AC: 555 AN: 4830

European-Finnish (FIN) AF: 0.191 AC: 2024 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14869 AN: 68014

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.210 Hom.: 407

Bravo AF: 0.196

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.46
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1010820; hg19: chr15-83614954;