13-46892589-C-T

Variant names:

• chr13-46892589-C-T
• ENST00000543956.5:c.-76G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000621.5(HTR2A):​c.414G>A​(p.Gly138Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HTR2A NM_000621.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.00004810
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.133
• Publications: 0 publications found

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ENSG00000301465 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.187327).
• BP6: Variant 13-46892589-C-T is Benign according to our data. Variant chr13-46892589-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3107497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.133 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.414G>A	p.Gly138Gly	splice_region synonymous	Exon 3 of 4	NP_000612.1	P28223-1
	HTR2A	NM_001165947.5		c.-76G>A		splice_region	Exon 2 of 3	NP_001159419.2	A0A7P0PKG8
	HTR2A	NM_001378924.1		c.414G>A	p.Gly138Gly	splice_region synonymous	Exon 3 of 4	NP_001365853.1	P28223-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000543956.5	TSL:1	c.-76G>A		splice_region	Exon 2 of 3	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.414G>A	p.Gly138Gly	splice_region synonymous	Exon 3 of 4	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.-76G>A		5_prime_UTR	Exon 2 of 3	ENSP00000441861.2	A0A7P0PKG8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.5
DANN	Uncertain	0.98
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.70	D
PhyloP100		-0.13
Vest4		0.92
GERP RS		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000048
dbscSNV1_RF	Benign	0.13
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

Other links and lift over

hg19: chr13-47466724; COSMIC: COSV66327030; COSMIC: COSV66327030;