10-113553047-AT-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001177660.3(HABP2):c.-10+2091del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,055,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: HABP2 NM_001177660.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_001177660.3	c.-10+2091del		intron_variant
HABP2	NM_004132.5			upstream_gene_variant		ENST00000351270.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000542051.5	c.-10+2091del		intron_variant		2
HABP2	ENST00000351270.4			upstream_gene_variant		1	NM_004132.5	P1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000342 AC: 309 AN: 903568 Hom.: 0 Cov.: 12 AF XY: 0.000356 AC XY: 167 AN XY: 469124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000440

Gnomad4 ASJ exome AF: 0.000908

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000411

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000405

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32 AN XY: 74436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000351

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Factor VII Marburg I Variant Thrombophilia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs768924245; hg19: chr10-115312806;