chr15-82849766-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004839.4(HOMER2):c.981C>T(p.Asp327=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,613,860 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 37 hom., cov: 33)
Exomes 𝑓: 0.026 ( 568 hom. )
Consequence
HOMER2
NM_004839.4 synonymous
NM_004839.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.38
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 15-82849766-G-A is Benign according to our data. Variant chr15-82849766-G-A is described in ClinVar as [Benign]. Clinvar id is 508610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.38 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0177 (2693/152224) while in subpopulation SAS AF= 0.0272 (131/4820). AF 95% confidence interval is 0.0257. There are 37 homozygotes in gnomad4. There are 1321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2693 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOMER2 | NM_004839.4 | c.981C>T | p.Asp327= | synonymous_variant | 9/9 | ENST00000450735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOMER2 | ENST00000450735.7 | c.981C>T | p.Asp327= | synonymous_variant | 9/9 | 1 | NM_004839.4 | ||
HOMER2 | ENST00000304231.12 | c.1014C>T | p.Asp338= | synonymous_variant | 9/9 | 5 | P1 | ||
HOMER2 | ENST00000558552.1 | n.861C>T | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
HOMER2 | ENST00000558090.2 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0177 AC: 2692AN: 152106Hom.: 37 Cov.: 33
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GnomAD3 exomes AF: 0.0197 AC: 4913AN: 249088Hom.: 74 AF XY: 0.0212 AC XY: 2862AN XY: 135144
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GnomAD4 exome AF: 0.0257 AC: 37547AN: 1461636Hom.: 568 Cov.: 31 AF XY: 0.0262 AC XY: 19019AN XY: 727096
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GnomAD4 genome AF: 0.0177 AC: 2693AN: 152224Hom.: 37 Cov.: 33 AF XY: 0.0177 AC XY: 1321AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 20, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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