dbSNP rs2046071: HOMER2:c.*8975C>T (chr15-82838299-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000558090.2(HOMER2):c.*8975C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,224 control chromosomes in the GnomAD database, including 17,264 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 0.47 ( 17244 hom., cov: 33)

Exomes 𝑓: 0.46 ( 20 hom. )

Consequence

HOMER2
ENST00000558090.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
HOMER2	XM_011522232.3 link	c.*27-505C>T	intron_variant	Intron 9 of 9	XP_011520534.1
HOMER2	XM_047433356.1 link	c.*27-505C>T	intron_variant	Intron 9 of 9	XP_047289312.1
HOMER2	XM_047433359.1 link	c.*27-505C>T	intron_variant	Intron 9 of 9	XP_047289315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000558090.2 link	c.*8975C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000452870.1

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71160

AN:

151930

Hom.:

17227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.460

AC:

AN:

176

Hom.:

Cov.:

AF XY:

0.424

AC XY:

AN XY:

132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.200

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.450

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.493

AC:

AN:

134

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.468

AC:

71228

AN:

152048

Hom.:

17244

Cov.:

AF XY:

0.464

AC XY:

34521

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.397

AC:

16442

AN:

41444

American (AMR)

AF:

0.514

AC:

7853

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

1875

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1211

AN:

5162

South Asian (SAS)

AF:

0.276

AC:

1331

AN:

4828

European-Finnish (FIN)

AF:

0.539

AC:

5698

AN:

10578

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35303

AN:

67960

Other (OTH)

AF:

0.479

AC:

1010

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.502

Hom.:

85760

Bravo

AF:

0.464

Asia WGS

AF:

0.268

AC:

934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

(source)

DANN

Benign

0.54

PhyloP100

1.1

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over