5-157106904-G-C

Variant names:

• chr5-157106904-G-C
• rs41283181
• ENST00000521665.2:c.-235C>G

Variant summary

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

The ENST00000521665.2(HAVCR2):​c.-235C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAVCR2 ENST00000521665.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 0 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

ENSG00000254246 (HGNC:):

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=0.074608356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521665.2. 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.117C>G	p.Phe39Leu	missense	Exon 2 of 7	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000521665.2	TSL:1	c.-235C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000513314.1	A0A8V8TMM7
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.117C>G	p.Phe39Leu	missense	Exon 2 of 7	ENSP00000312002.4	Q8TDQ0-1
	HAVCR2	ENST00000521665.2	TSL:1	c.-235C>G		5_prime_UTR	Exon 1 of 4	ENSP00000513314.1	A0A8V8TMM7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.8
DANN	Benign	0.65
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.096	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.40
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.035
Sift	Benign	0.26	T
Sift4G	Benign	0.65	T
Varity_R		0.18
gMVP		0.72
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41283181;

hg19: chr5-156533915;