Variant 5-175683324-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367711.1(HRH2):c.91A>T(p.Ile31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HRH2
NM_001367711.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0100

Variant links:

Genes affected

HRH2 (HGNC:5183): (histamine receptor H2) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. Histamine receptor H2 belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

HRH2 links:

HRH2 (HGNC:):

HRH2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07149154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH2	NM_001367711.1 linkuse as main transcript	c.91A>T	p.Ile31Phe	missense_variant	2/3	ENST00000636584.2	NP_001354640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HRH2	ENST00000636584.2 linkuse as main transcript	c.91A>T	p.Ile31Phe	missense_variant	2/3	3	NM_001367711.1	ENSP00000489742.1	A0A1B0GTK7
HRH2	ENST00000377291.2 linkuse as main transcript	c.91A>T	p.Ile31Phe	missense_variant	2/3	1		ENSP00000366506.2	P25021-2
HRH2	ENST00000624694.2 linkuse as main transcript	n.91A>T		non_coding_transcript_exon_variant	1/3	5		ENSP00000490705.1	A0A1B0GVZ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251494

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.91A>T (p.I31F) alteration is located in exon 1 (coding exon 1) of the HRH2 gene. This alteration results from a A to T substitution at nucleotide position 91, causing the isoleucine (I) at amino acid position 31 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.8

DANN

Benign

0.92

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;.;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.088

Sift

Benign

0.95

T;.;T

Sift4G

Benign

0.88

T;.;T

Polyphen

0.0040

.;.;B

Vest4

0.13

MutPred

0.57

Gain of catalytic residue at I31 (P = 0.0349);Gain of catalytic residue at I31 (P = 0.0349);Gain of catalytic residue at I31 (P = 0.0349);

MVP

0.63

MPC

2.1

ClinPred

0.14

GERP RS

-1.2

Varity_R

0.073

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over