chr5-157087175-T-G

Variant names:

• chr5-157087175-T-G
• rs767274710
• NM_032782.5:c.833A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032782.5(HAVCR2):​c.833A>C​(p.Asn278Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 1 publications found

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

ACMG classification

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=0.081751674).

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>C	p.Asn278Thr	missense	Exon 7 of 7	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.833A>C	p.Asn278Thr	missense	Exon 7 of 7	ENSP00000312002.4	Q8TDQ0-1
	HAVCR2	ENST00000696899.1		c.833A>C	p.Asn278Thr	missense	Exon 8 of 8	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.833A>C	p.Asn278Thr	missense	Exon 8 of 8	ENSP00000523303.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.0
DANN	Benign	0.57
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.22
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.0
Sift	Benign	0.25	T
Sift4G	Benign	0.24	T
Polyphen		0.080	B
Vest4		0.15
MutPred		0.20		Gain of phosphorylation at N278 (P = 0.0429)
MVP		0.040
MPC		0.13
ClinPred		0.031	T
GERP RS		0.60
Varity_R		0.055
gMVP		0.56
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767274710; hg19: chr5-156514186;