15-82849773-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP3 BP6_Moderate

The NM_004839.4(HOMER2):c.974A>G(p.Lys325Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HOMER2 NM_004839.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784
• BP6: Variant 15-82849773-T-C is Benign according to our data. Variant chr15-82849773-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2831943.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4	c.974A>G	p.Lys325Arg	missense_variant	9/9	ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7	c.974A>G	p.Lys325Arg	missense_variant	9/9	1	NM_004839.4
HOMER2	ENST00000304231.12	c.1007A>G	p.Lys336Arg	missense_variant	9/9	5		P1
HOMER2	ENST00000558552.1	n.854A>G		non_coding_transcript_exon_variant	3/3	2
HOMER2	ENST00000558090.2			upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Uncertain	0.12	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.16
Sift	Benign	0.27	T;T
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.69
MutPred		0.17		.;Loss of ubiquitination at K336 (P = 0.0148);
MVP		0.82
MPC		0.77
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-83518525;