Genetic Variant NM_032782.5:c.833A>T (chr5-157087175-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032782.5(HAVCR2):c.833A>T(p.Asn278Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N278S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

HAVCR2
NM_032782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.218

Publications

0 publications found

Variant links:

Genes affected

HAVCR2 (HGNC:18437): (hepatitis A virus cellular receptor 2) The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

HAVCR2 Gene-Disease associations (from GenCC):

subcutaneous panniculitis-like T-cell lymphoma
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
HAVCR2-related cancer predisposition
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

HAVCR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116978705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	NM_032782.5	MANE Select	c.833A>T	p.Asn278Ile	missense	Exon 7 of 7	NP_116171.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.833A>T	p.Asn278Ile	missense	Exon 7 of 7	ENSP00000312002.4	Q8TDQ0-1
HAVCR2	ENST00000696899.1		c.833A>T	p.Asn278Ile	missense	Exon 8 of 8	ENSP00000512960.1	Q8TDQ0-1
HAVCR2	ENST00000853244.1		c.833A>T	p.Asn278Ile	missense	Exon 8 of 8	ENSP00000523303.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0072

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.69

M_CAP

Benign

0.0046

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.22

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

REVEL

Benign

0.021

Sift

Benign

0.063

Sift4G

Uncertain

0.035

Polyphen

0.38

Vest4

0.20

MutPred

0.34

Loss of disorder (P = 0.0185)

MVP

0.11

MPC

0.17

ClinPred

0.093

GERP RS

0.60

Varity_R

0.11

gMVP

0.72

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over