chr5-157098909-AAGAG-A

Position:

• chr5-157098909-AAGAG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_032782.5(HAVCR2):​c.479-12_479-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,520,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: HAVCR2 NM_032782.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.279

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-157098909-AAGAG-A is Benign according to our data. Variant chr5-157098909-AAGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR2	NM_032782.5	c.479-12_479-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000307851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000307851.9	c.479-12_479-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032782.5	P2

Frequencies

GnomAD3 genomes AF: 0.000174 AC: 26 AN: 149280 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000402

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000596

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00176 AC: 2409 AN: 1371010 Hom.: 0 AF XY: 0.00179 AC XY: 1220 AN XY: 682146

Gnomad4 AFR exome AF: 0.00193

Gnomad4 AMR exome AF: 0.00396

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.00288

Gnomad4 FIN exome AF: 0.00177

Gnomad4 NFE exome AF: 0.00159

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.000174 AC: 26 AN: 149358 Hom.: 0 Cov.: 32 AF XY: 0.000192 AC XY: 14 AN XY: 72888

Gnomad4 AFR AF: 0.000341

Gnomad4 AMR AF: 0.000402

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000596

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

HAVCR2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

HAVCR2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs70984443; hg19: chr5-156525920;