15-82854635-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004839.4(HOMER2):c.651+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,608,334 control chromosomes in the GnomAD database, including 6,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 839 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5653 hom. )

Consequence

HOMER2
NM_004839.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.130

Publications

11 publications found

Variant links:

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

HOMER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 15-82854635-C-T is Benign according to our data. Variant chr15-82854635-C-T is described in ClinVar as Benign. ClinVar VariationId is 508119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4 link	c.651+9G>A		intron_variant	Intron 6 of 8	ENST00000450735.7	NP_004830.2	Q9NSB8-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOMER2	ENST00000450735.7 link	c.651+9G>A	intron_variant	Intron 6 of 8	1	NM_004839.4	ENSP00000407634.2	Q9NSB8-2
HOMER2	ENST00000304231.12 link	c.684+9G>A	intron_variant	Intron 6 of 8	5		ENSP00000305632.8	Q9NSB8-1
HOMER2	ENST00000558817.1 link	c.408+9G>A	intron_variant	Intron 3 of 4	3		ENSP00000454125.1	H0YNR9
HOMER2	ENST00000561345.5 link	n.*60G>A	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0973

AC:

14791

AN:

152056

Hom.:

834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0809

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.0445

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0726

Gnomad OTH

AF:

0.0964

GnomAD2 exomes

AF:

0.0952

AC:

23215

AN:

243976

AF XY:

0.0887

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0704

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.0813

AC:

118336

AN:

1456160

Hom.:

5653

Cov.:

AF XY:

0.0799

AC XY:

57849

AN XY:

723798

show subpopulations

African (AFR)

AF:

0.123

AC:

4095

AN:

33420

American (AMR)

AF:

0.171

AC:

7579

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

2201

AN:

26034

East Asian (EAS)

AF:

0.225

AC:

8876

AN:

39530

South Asian (SAS)

AF:

0.0453

AC:

3890

AN:

85786

European-Finnish (FIN)

AF:

0.0667

AC:

3445

AN:

51626

Middle Eastern (MID)

AF:

0.106

AC:

610

AN:

5748

European-Non Finnish (NFE)

AF:

0.0741

AC:

82228

AN:

1109460

Other (OTH)

AF:

0.0899

AC:

5412

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

5678

11357

17035

22714

28392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3262

6524

9786

13048

16310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0974

AC:

14817

AN:

152174

Hom.:

839

Cov.:

AF XY:

0.0980

AC XY:

7288

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.120

AC:

4997

AN:

41532

American (AMR)

AF:

0.151

AC:

2307

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0809

AC:

281

AN:

3472

East Asian (EAS)

AF:

0.205

AC:

1056

AN:

5154

South Asian (SAS)

AF:

0.0446

AC:

215

AN:

4824

European-Finnish (FIN)

AF:

0.0677

AC:

717

AN:

10590

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0726

AC:

4938

AN:

67998

Other (OTH)

AF:

0.0958

AC:

202

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

677

1353

2030

2706

3383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0822

Hom.:

858

Bravo

AF:

0.104

Asia WGS

AF:

0.0970

AC:

339

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Sep 11, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 10, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.7

(source)

DANN

Benign

0.62

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over