5-157098909-AAGAG-A

Variant names:

• chr5-157098909-AAGAG-A
• rs70984443
• NM_032782.5:c.479-12_479-9delCTCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_032782.5(HAVCR2):​c.479-12_479-9delCTCT variant causes a 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: HAVCR2 NM_032782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.279
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-157098909-AAGAG-A is Benign according to our data. Variant chr5-157098909-AAGAG-A is described in ClinVar as Benign. ClinVar VariationId is 2655989.Status of the report is criteria_provided_single_submitter, 1 stars.

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.479-12_479-9delCTCT		intron	N/A	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.479-12_479-9delCTCT		intron	N/A	ENSP00000312002.4	Q8TDQ0-1
	HAVCR2	ENST00000521665.2	TSL:1	c.128-12_128-9delCTCT		intron	N/A	ENSP00000513314.1	A0A8V8TMM7
	HAVCR2	ENST00000696899.1		c.479-12_479-9delCTCT		intron	N/A	ENSP00000512960.1	Q8TDQ0-1

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

GnomAD2 exomes AF: 0.00329 AC: 466 AN: 141594 AF XY: 0.00321

Gnomad AFR exome AF: 0.00199

Gnomad AMR exome AF: 0.00588

Gnomad ASJ exome AF: 0.00366

Gnomad EAS exome AF: 0.00216

Gnomad FIN exome AF: 0.00331

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00472

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00193 AC: 60 AN: 31102

American (AMR) AF: 0.00396 AC: 163 AN: 41110

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 47 AN: 24088

East Asian (EAS) AF: 0.00105 AC: 39 AN: 37022

South Asian (SAS) AF: 0.00288 AC: 231 AN: 80114

European-Finnish (FIN) AF: 0.00177 AC: 87 AN: 49132

Middle Eastern (MID) AF: 0.00181 AC: 10 AN: 5510

European-Non Finnish (NFE) AF: 0.00159 AC: 1668 AN: 1046672

Other (OTH) AF: 0.00185 AC: 104 AN: 56260

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.000341 AC: 14 AN: 40996

American (AMR) AF: 0.000402 AC: 6 AN: 14926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5132

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000596 AC: 4 AN: 67094

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00626 Hom.: 0

Bravo AF: 0.000261

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	HAVCR2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs70984443; hg19: chr5-156525920;