10-113553051-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001177660.3(HABP2):c.-10+2090T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,074,398 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (5 hom.)
• Consequence: HABP2 NM_001177660.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.583

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-113553051-T-C is Benign according to our data. Variant chr10-113553051-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 298891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_001177660.3	c.-10+2090T>C		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+2090T>C		intron_variant		2
HABP2	ENST00000351270.4			upstream_gene_variant		1	NM_004132.5	P1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152096 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00114 AC: 1055 AN: 922184 Hom.: 5 Cov.: 12 AF XY: 0.00106 AC XY: 505 AN XY: 477852

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000958

Gnomad4 ASJ exome AF: 0.00186

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000681

Gnomad4 FIN exome AF: 0.000342

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.000992

GnomAD4 genome AF: 0.00365 AC: 555 AN: 152214 Hom.: 1 Cov.: 33 AF XY: 0.00355 AC XY: 264 AN XY: 74434

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000837 Hom.: 0

Bravo AF: 0.00459

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2020

See Variant Classification Assertion Criteria. -

Factor VII Marburg I Variant Thrombophilia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.0
Dann	Benign	0.82

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: rs11575695; hg19: chr10-115312810; COSMIC: COSV63636845;