dbSNP rs2760351: HTR2A:c.614-20541T>C (chr13-46856180-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000621.5(HTR2A):c.614-20541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,106 control chromosomes in the GnomAD database, including 35,215 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 0.67 ( 35215 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

HTR2A
NM_000621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

1 publications found

Variant links:

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]

HTR2A links:

HTR2A-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

HTR2A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.614-20541T>C		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1	P28223-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTR2A	ENST00000542664.4 link	c.614-20541T>C	intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1	P28223-1
HTR2A	ENST00000543956.5 link	c.125-20541T>C	intron_variant	Intron 2 of 2	1		ENSP00000441861.2	A0A7P0PKG8
HTR2A-AS1	ENST00000430913.3 link	n.403A>G	non_coding_transcript_exon_variant	Exon 4 of 4	3
HTR2A-AS1	ENST00000455126.5 link	n.175A>G	non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102469

AN:

151986

Hom.:

35187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.668

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.674

AC:

102537

AN:

152104

Hom.:

35215

Cov.:

AF XY:

0.684

AC XY:

50877

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.608

AC:

25215

AN:

41470

American (AMR)

AF:

0.739

AC:

11292

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2382

AN:

3470

East Asian (EAS)

AF:

0.989

AC:

5129

AN:

5184

South Asian (SAS)

AF:

0.905

AC:

4360

AN:

4820

European-Finnish (FIN)

AF:

0.706

AC:

7457

AN:

10562

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.655

AC:

44500

AN:

67990

Other (OTH)

AF:

0.671

AC:

1418

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1665

3330

4995

6660

8325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.667

Hom.:

11008

Bravo

AF:

0.672

Asia WGS

AF:

0.914

AC:

3176

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.1

(source)

DANN

Benign

0.43

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over