rs1036199

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032782.5(HAVCR2):c.419G>T(p.Arg140Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,600,776 control chromosomes in the GnomAD database, including 558,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.83 ( 53089 hom., cov: 33)

Exomes 𝑓: 0.83 ( 505713 hom. )

Consequence

HAVCR2
NM_032782.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.202

Publications

73 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 links:

ENSG00000254246 (HGNC:):

ENSG00000254246 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.7537273E-7).

BP6

Variant 5-157104725-C-A is Benign according to our data. Variant chr5-157104725-C-A is described in ClinVar as Benign. ClinVar VariationId is 1285330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR2	NM_032782.5 link	c.419G>T	p.Arg140Leu	missense_variant	Exon 3 of 7	ENST00000307851.9	NP_116171.3	Q8TDQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000307851.9 link	c.419G>T	p.Arg140Leu	missense_variant	Exon 3 of 7	1	NM_032782.5	ENSP00000312002.4		Q8TDQ0-1

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126877

AN:

152096

Hom.:

53052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.853

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.838

GnomAD2 exomes

AF:

0.865

AC:

203321

AN:

234978

AF XY:

0.868

show subpopulations

Gnomad AFR exome

AF:

0.806

Gnomad AMR exome

AF:

0.924

Gnomad ASJ exome

AF:

0.883

Gnomad EAS exome

AF:

0.989

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.815

Gnomad OTH exome

AF:

0.850

GnomAD4 exome

AF:

0.834

AC:

1208317

AN:

1448562

Hom.:

505713

Cov.:

AF XY:

0.837

AC XY:

602396

AN XY:

719370

show subpopulations

African (AFR)

AF:

0.802

AC:

26731

AN:

33318

American (AMR)

AF:

0.919

AC:

39888

AN:

43404

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

22680

AN:

25682

East Asian (EAS)

AF:

0.983

AC:

38898

AN:

39588

South Asian (SAS)

AF:

0.951

AC:

79997

AN:

84162

European-Finnish (FIN)

AF:

0.838

AC:

44145

AN:

52696

Middle Eastern (MID)

AF:

0.833

AC:

4774

AN:

5730

European-Non Finnish (NFE)

AF:

0.816

AC:

900587

AN:

1104120

Other (OTH)

AF:

0.846

AC:

50617

AN:

59862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

8980

17960

26941

35921

44901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20912

41824

62736

83648

104560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.834

AC:

126972

AN:

152214

Hom.:

53089

Cov.:

AF XY:

0.840

AC XY:

62552

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.801

AC:

33268

AN:

41516

American (AMR)

AF:

0.887

AC:

13562

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.888

AC:

3079

AN:

3468

East Asian (EAS)

AF:

0.987

AC:

5117

AN:

5184

South Asian (SAS)

AF:

0.952

AC:

4597

AN:

4828

European-Finnish (FIN)

AF:

0.853

AC:

9048

AN:

10604

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.816

AC:

55468

AN:

68012

Other (OTH)

AF:

0.840

AC:

1771

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1069

2138

3208

4277

5346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.827

Hom.:

229843

Bravo

AF:

0.836

TwinsUK

AF:

0.818

AC:

3034

ALSPAC

AF:

0.814

AC:

3136

ESP6500AA

AF:

0.811

AC:

3573

ESP6500EA

AF:

0.813

AC:

6994

ExAC

AF:

0.857

AC:

103696

Asia WGS

AF:

0.955

AC:

3321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Subcutaneous panniculitis-like T-cell lymphoma

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.9

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

8.8e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.

PhyloP100

0.20

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.019

Sift

Benign

0.47

T;T

Sift4G

Benign

0.37

T;.

Polyphen

0.0

B;.

Vest4

0.015

MPC

0.16

ClinPred

0.0017

GERP RS

-0.064

Varity_R

0.040

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over