rs2306428

Variant names:

• chr15-82854635-C-A
• rs2306428
• NM_004839.4:c.651+9G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82854635-C-A
• chr15-82854635-C-G
• chr15-82854635-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004839.4(HOMER2):​c.651+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,354 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.651+9G>T		intron_variant	Intron 6 of 8	ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.651+9G>T		intron_variant	Intron 6 of 8	1	NM_004839.4	ENSP00000407634.2
HOMER2	ENST00000304231.12	c.684+9G>T		intron_variant	Intron 6 of 8	5		ENSP00000305632.8
HOMER2	ENST00000558817.1	c.408+9G>T		intron_variant	Intron 3 of 4	3		ENSP00000454125.1
HOMER2	ENST00000561345.5	n.*60G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456354 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723904

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109546

Other (OTH) AF: 0.00 AC: 0 AN: 60222

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.67
PhyloP100		-0.13

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: rs2306428; hg19: chr15-83523387;