rs1256429

Variant names:

• chr15-82852284-C-G
• rs1256429
• NM_004839.4:c.652-32G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-82852284-C-G
• chr15-82852284-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.652-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 18 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.652-32G>C		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.652-32G>C		intron_variant	Intron 6 of 8	1	NM_004839.4	ENSP00000407634.2
HOMER2	ENST00000558552.1	n.500G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
HOMER2	ENST00000304231.12	c.685-32G>C		intron_variant	Intron 6 of 8	5		ENSP00000305632.8
HOMER2	ENST00000558817.1	c.409-32G>C		intron_variant	Intron 3 of 4	3		ENSP00000454125.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1335692 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 671252

African (AFR) AF: 0.00 AC: 0 AN: 30956

American (AMR) AF: 0.00 AC: 0 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 83176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 999672

Other (OTH) AF: 0.00 AC: 0 AN: 56210

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0090
DANN	Benign	0.41
PhyloP100		0.0070

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: rs1256429; hg19: chr15-83521036;