chr15-82875096-C-A

Variant names:

• chr15-82875096-C-A
• rs1256453
• NM_004839.4:c.294+177G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004839.4(HOMER2):​c.294+177G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,088 control chromosomes in the GnomAD database, including 30,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30203 hom., cov: 32)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.402
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 15-82875096-C-A is Benign according to our data. Variant chr15-82875096-C-A is described in ClinVar as Benign. ClinVar VariationId is 1237323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.294+177G>T		intron_variant	Intron 3 of 8	ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.294+177G>T		intron_variant	Intron 3 of 8	1	NM_004839.4	ENSP00000407634.2
HOMER2	ENST00000304231.12	c.294+177G>T		intron_variant	Intron 3 of 8	5		ENSP00000305632.8
HOMER2	ENST00000560374.5	n.623+177G>T		intron_variant	Intron 3 of 3	3
HOMER2	ENST00000561345.5	n.353+177G>T		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94597 AN: 151970 Hom.: 30158 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94701 AN: 152088 Hom.: 30203 Cov.: 32 AF XY: 0.625 AC XY: 46418 AN XY: 74328

African (AFR) AF: 0.750 AC: 31132 AN: 41492

American (AMR) AF: 0.622 AC: 9504 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2025 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4304 AN: 5176

South Asian (SAS) AF: 0.536 AC: 2581 AN: 4812

European-Finnish (FIN) AF: 0.554 AC: 5859 AN: 10574

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37341 AN: 67968

Other (OTH) AF: 0.623 AC: 1315 AN: 2112

Alfa AF: 0.479 Hom.: 1483

Bravo AF: 0.635

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 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	-0.98
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		0.40
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: rs1256453; hg19: chr15-83543848;