rs2240879

Variant names:

• chr10-113553052-T-A
• rs2240879
• NM_001177660.3:c.-10+2091T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113553052-T-A
• chr10-113553052-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001177660.3(HABP2):​c.-10+2091T>A variant causes a intron 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HABP2 NM_001177660.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 0 publications found

Genes affected

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HABP2	NM_001177660.3	c.-10+2091T>A		intron_variant	Intron 1 of 12		NP_001171131.1
HABP2	NM_004132.5	c.-70T>A		upstream_gene_variant		ENST00000351270.4	NP_004123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000542051.5	c.-10+2091T>A		intron_variant	Intron 1 of 12	2		ENSP00000443283.1
HABP2	ENST00000351270.4	c.-70T>A		upstream_gene_variant		1	NM_004132.5	ENSP00000277903.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 917390 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 475086

African (AFR) AF: 0.00 AC: 0 AN: 22616

American (AMR) AF: 0.00 AC: 0 AN: 40428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22008

East Asian (EAS) AF: 0.00 AC: 0 AN: 36928

South Asian (SAS) AF: 0.00 AC: 0 AN: 72882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 623076

Other (OTH) AF: 0.00 AC: 0 AN: 42172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		-1.8
PromoterAI		-0.040	Neutral

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: rs2240879; hg19: chr10-115312811;