dbSNP rs767274710: HAVCR2:p.Asn278Ile (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:

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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

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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