15-82852284-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004839.4(HOMER2):​c.652-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,486,134 control chromosomes in the GnomAD database, including 462,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52004 hom., cov: 33)
  • Exomes 𝑓: 0.78 (409999 hom.)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-82852284-C-T is Benign according to our data. Variant chr15-82852284-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125336 AN: 152142 Hom.: 51939 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.809

GnomAD2 exomes AF: 0.795 AC: 193514 AN: 243430 AF XY: 0.783

Gnomad AFR exome AF: 0.924

Gnomad AMR exome AF: 0.897

Gnomad ASJ exome AF: 0.761

Gnomad EAS exome AF: 0.816

Gnomad FIN exome AF: 0.791

Gnomad NFE exome AF: 0.783

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.782 AC: 1043047 AN: 1333874 Hom.: 409999 Cov.: 18 AF XY: 0.777 AC XY: 520845 AN XY: 670376

African (AFR) AF: 0.927 AC: 28679 AN: 30934

American (AMR) AF: 0.890 AC: 39035 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 19104 AN: 25136

East Asian (EAS) AF: 0.842 AC: 32758 AN: 38922

South Asian (SAS) AF: 0.661 AC: 54925 AN: 83104

European-Finnish (FIN) AF: 0.791 AC: 41239 AN: 52168

Middle Eastern (MID) AF: 0.749 AC: 4126 AN: 5510

European-Non Finnish (NFE) AF: 0.781 AC: 779610 AN: 998112

Other (OTH) AF: 0.776 AC: 43571 AN: 56148

GnomAD4 genome AF: 0.824 AC: 125460 AN: 152260 Hom.: 52004 Cov.: 33 AF XY: 0.822 AC XY: 61152 AN XY: 74438

African (AFR) AF: 0.921 AC: 38291 AN: 41588

American (AMR) AF: 0.850 AC: 13000 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2662 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4286 AN: 5178

South Asian (SAS) AF: 0.655 AC: 3158 AN: 4818

European-Finnish (FIN) AF: 0.788 AC: 8354 AN: 10598

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53172 AN: 67996

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.798 Hom.: 150229

Bravo AF: 0.837

Asia WGS AF: 0.775 AC: 2692 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.017
DANN	Benign	0.35
PhyloP100		0.0070
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: rs1256429; hg19: chr15-83521036; COSMIC: COSV58487674; COSMIC: COSV58487674;