rs2070040

Variant names:

• chr13-46893491-G-A
• rs2070040
• NM_000621.5:c.413-901C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.413-901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,102 control chromosomes in the GnomAD database, including 11,775 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 0.37 (11775 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.413-901C>T		intron_variant	Intron 2 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.413-901C>T		intron_variant	Intron 2 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.-77-901C>T		intron_variant	Intron 1 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.413-901C>T		intron_variant	Intron 2 of 3	1	NM_000621.5	ENSP00000437737.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56460 AN: 151984 Hom.: 11774 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.371 AC: 56489 AN: 152102 Hom.: 11775 Cov.: 32 AF XY: 0.375 AC XY: 27897 AN XY: 74324

African (AFR) AF: 0.189 AC: 7834 AN: 41510

American (AMR) AF: 0.448 AC: 6853 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1828 AN: 5162

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4820

European-Finnish (FIN) AF: 0.521 AC: 5502 AN: 10556

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30167 AN: 67964

Other (OTH) AF: 0.337 AC: 713 AN: 2114

Alfa AF: 0.412 Hom.: 19875

Bravo AF: 0.360

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.43
PhyloP100		-0.93
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: rs2070040; hg19: chr13-47467626;