15-82849543-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004839.4(HOMER2):c.*172C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 606,058 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (38 hom.)
• Consequence: HOMER2 NM_004839.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-82849543-G-A is Benign according to our data. Variant chr15-82849543-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1320602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00619 (2810/453766) while in subpopulation SAS AF= 0.017 (711/41766). AF 95% confidence interval is 0.016. There are 38 homozygotes in gnomad4_exome. There are 1618 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.
• BS2: High AC in GnomAd at 702 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4	c.*172C>T		3_prime_UTR_variant	9/9	ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7	c.*172C>T		3_prime_UTR_variant	9/9	1	NM_004839.4
HOMER2	ENST00000558090.2	c.*26+146C>T		intron_variant		1
HOMER2	ENST00000304231.12	c.*172C>T		3_prime_UTR_variant	9/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.00461 AC: 702 AN: 152174 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00619 AC: 2810 AN: 453766 Hom.: 38 Cov.: 5 AF XY: 0.00683 AC XY: 1618 AN XY: 236754

Gnomad4 AFR exome AF: 0.000476

Gnomad4 AMR exome AF: 0.000390

Gnomad4 ASJ exome AF: 0.000220

Gnomad4 EAS exome AF: 0.0000974

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0257

Gnomad4 NFE exome AF: 0.00418

Gnomad4 OTH exome AF: 0.00494

GnomAD4 genome AF: 0.00462 AC: 703 AN: 152292 Hom.: 11 Cov.: 33 AF XY: 0.00594 AC XY: 442 AN XY: 74466

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.00388

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00350 Hom.: 0

Bravo AF: 0.00175

Asia WGS AF: 0.00577 AC: 20 AN: 3478

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

GeneDx

Jan 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	2.2
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs79958469; hg19: chr15-83518295;