rs2770292

Variant names:

• chr13-46860971-C-G
• rs2770292
• NM_000621.5:c.614-25332G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-46860971-C-G
• chr13-46860971-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000621.5(HTR2A):​c.614-25332G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,082 control chromosomes in the GnomAD database, including 2,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2528 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

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.614-25332G>C		intron	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.614-25332G>C		intron	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.125-25332G>C		intron	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.614-25332G>C		intron	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.125-25332G>C		intron	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.614-25332G>C		intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26394 AN: 151964 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26417 AN: 152082 Hom.: 2528 Cov.: 32 AF XY: 0.171 AC XY: 12683 AN XY: 74328

African (AFR) AF: 0.142 AC: 5897 AN: 41490

American (AMR) AF: 0.206 AC: 3152 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3468

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5180

South Asian (SAS) AF: 0.101 AC: 486 AN: 4822

European-Finnish (FIN) AF: 0.206 AC: 2177 AN: 10552

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13462 AN: 67964

Other (OTH) AF: 0.148 AC: 312 AN: 2110

Alfa AF: 0.110 Hom.: 207

Bravo AF: 0.174

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.69
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2770292; hg19: chr13-47435106;