rs864309524
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_004839.4(HOMER2):c.554G>C(p.Arg185Pro) 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 Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R185Q) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
HOMER2
NM_004839.4 missense
NM_004839.4 missense
Scores
9
7
1
Clinical Significance
Conservation
PhyloP100: 5.53
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.796
PP5
?
Variant 15-82854741-C-G is Pathogenic according to our data. Variant chr15-82854741-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 218351.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-82854741-C-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOMER2 | NM_004839.4 | c.554G>C | p.Arg185Pro | missense_variant | 6/9 | ENST00000450735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOMER2 | ENST00000450735.7 | c.554G>C | p.Arg185Pro | missense_variant | 6/9 | 1 | NM_004839.4 | ||
HOMER2 | ENST00000304231.12 | c.587G>C | p.Arg196Pro | missense_variant | 6/9 | 5 | P1 | ||
HOMER2 | ENST00000558817.1 | c.311G>C | p.Arg104Pro | missense_variant | 3/5 | 3 | |||
HOMER2 | ENST00000561345.5 | n.613G>C | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 68 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
0.34
.;Loss of methylation at R196 (P = 0.0183);.;
MVP
MPC
0.99
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at