chr15-82849743-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004839.4(HOMER2):c.1004G>A(p.Gly335Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000275 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
HOMER2
NM_004839.4 missense
NM_004839.4 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 5.43
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOMER2 | NM_004839.4 | c.1004G>A | p.Gly335Glu | missense_variant | 9/9 | ENST00000450735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOMER2 | ENST00000450735.7 | c.1004G>A | p.Gly335Glu | missense_variant | 9/9 | 1 | NM_004839.4 | ||
HOMER2 | ENST00000304231.12 | c.1037G>A | p.Gly346Glu | missense_variant | 9/9 | 5 | P1 | ||
HOMER2 | ENST00000558552.1 | n.884G>A | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
HOMER2 | ENST00000558090.2 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000137 AC: 34AN: 248740Hom.: 0 AF XY: 0.0000963 AC XY: 13AN XY: 134966
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GnomAD4 exome AF: 0.000289 AC: 422AN: 1461578Hom.: 0 Cov.: 31 AF XY: 0.000253 AC XY: 184AN XY: 727058
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.1037G>A (p.G346E) alteration is located in exon 9 (coding exon 9) of the HOMER2 gene. This alteration results from a G to A substitution at nucleotide position 1037, causing the glycine (G) at amino acid position 346 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 335 of the HOMER2 protein (p.Gly335Glu). This variant is present in population databases (rs368481727, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with HOMER2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1420504). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.98
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at