dbSNP rs6305: HTR2A:p.Asp172Asp (chr13-46892487-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000621.5(HTR2A):c.516C>T(p.Asp172Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,614,218 control chromosomes in the GnomAD database, including 446 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 0.017 ( 32 hom., cov: 33)

Exomes 𝑓: 0.022 ( 414 hom. )

Consequence

HTR2A
NM_000621.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

46 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:

ENSG00000301465 (HGNC:):

ENSG00000301465 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=1.12 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HTR2A	NM_000621.5 link	c.516C>T	p.Asp172Asp	synonymous_variant	Exon 3 of 4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 link	c.516C>T	p.Asp172Asp	synonymous_variant	Exon 3 of 4		NP_001365853.1
HTR2A	NM_001165947.5 link	c.27C>T	p.Asp9Asp	synonymous_variant	Exon 2 of 3		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.516C>T	p.Asp172Asp	synonymous_variant	Exon 3 of 4	1	NM_000621.5	ENSP00000437737.1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2631

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00497

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0183

AC:

4601

AN:

251492

AF XY:

0.0188

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0456

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.0270

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0220

AC:

32154

AN:

1461874

Hom.:

414

Cov.:

AF XY:

0.0222

AC XY:

16134

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00466

AC:

156

AN:

33480

American (AMR)

AF:

0.0152

AC:

678

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

1169

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00896

AC:

773

AN:

86258

European-Finnish (FIN)

AF:

0.00545

AC:

291

AN:

53420

Middle Eastern (MID)

AF:

0.0577

AC:

333

AN:

5768

European-Non Finnish (NFE)

AF:

0.0246

AC:

27363

AN:

1111992

Other (OTH)

AF:

0.0230

AC:

1388

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1856

3712

5569

7425

9281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

968

1936

2904

3872

4840

<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:

0.0172

AC:

2626

AN:

152344

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1183

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00498

AC:

207

AN:

41590

American (AMR)

AF:

0.0191

AC:

292

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00580

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0268

AC:

1820

AN:

68024

Other (OTH)

AF:

0.0289

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

124

248

372

496

620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0226

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0317

EpiControl

AF:

0.0318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.0

(source)

DANN

Benign

0.73

PhyloP100

1.1

Mutation Taster

=91/9

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

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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