5-175683556-A-G

Position:

• chr5-175683556-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367711.1(HRH2):​c.323A>G​(p.Asn108Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HRH2 NM_001367711.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH2	NM_001367711.1	c.323A>G	p.Asn108Ser	missense_variant	2/3	ENST00000636584.2	NP_001354640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH2	ENST00000636584.2	c.323A>G	p.Asn108Ser	missense_variant	2/3	3	NM_001367711.1	ENSP00000489742.1
HRH2	ENST00000377291.2	c.323A>G	p.Asn108Ser	missense_variant	2/3	1		ENSP00000366506.2
HRH2	ENST00000624694.2	n.323A>G		non_coding_transcript_exon_variant	1/3	5		ENSP00000490705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.323A>G (p.N108S) alteration is located in exon 1 (coding exon 1) of the HRH2 gene. This alteration results from a A to G substitution at nucleotide position 323, causing the asparagine (N) at amino acid position 108 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L;.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D;.;D
REVEL	Benign	0.15
Sift	Benign	0.058	T;.;T
Sift4G	Uncertain	0.048	D;.;T
Polyphen		0.89	.;.;P
Vest4		0.53
MutPred		0.64		Loss of stability (P = 0.1912);Loss of stability (P = 0.1912);Loss of stability (P = 0.1912);
MVP		0.63
MPC		1.6
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-175110559;