NM_021828.5:c.*69C>A

Variant names:

• chr10-98459505-G-T
• rs35712968
• NM_021828.5:c.*69C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021828.5(HPSE2):​c.*69C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,511,974 control chromosomes in the GnomAD database, including 1,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (205 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1223 hom.)
• Consequence: HPSE2 NM_021828.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.66
• Publications: 5 publications found

Genes affected

HPSE2 (HGNC:18374): (heparanase 2 (inactive)) This gene encodes a heparanase enzyme. The encoded protein is a endoglycosidase that degrades heparin sulfate proteoglycans located on the extracellular matrix and cell surface. This protein may be involved in biological processes involving remodeling of the extracellular matrix including angiogenesis and tumor progression. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

HPSE2 Gene-Disease associations (from GenCC):

• urofacial syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Ochoa syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-98459505-G-T is Benign according to our data. Variant chr10-98459505-G-T is described in ClinVar as Benign. ClinVar VariationId is 1237632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021828.5. 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
	HPSE2	NM_021828.5	MANE Select	c.*69C>A		3_prime_UTR	Exon 12 of 12	NP_068600.4
	HPSE2	NM_001166246.1		c.*271C>A		3_prime_UTR	Exon 13 of 13	NP_001159718.1	Q8WWQ2-2
	HPSE2	NM_001166244.1		c.*69C>A		3_prime_UTR	Exon 11 of 11	NP_001159716.1	Q8WWQ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	ENST00000370552.8	TSL:1 MANE Select	c.*69C>A		3_prime_UTR	Exon 12 of 12	ENSP00000359583.3	Q8WWQ2-1
	HPSE2	ENST00000370549.5	TSL:1	c.*69C>A		3_prime_UTR	Exon 11 of 11	ENSP00000359580.1	Q8WWQ2-3
	HPSE2	ENST00000628193.2	TSL:1	c.*69C>A		3_prime_UTR	Exon 10 of 10	ENSP00000485916.1	Q8WWQ2-4

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6988 AN: 152032 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0386 AC: 52497 AN: 1359824 Hom.: 1223 Cov.: 21 AF XY: 0.0383 AC XY: 26141 AN XY: 681972

African (AFR) AF: 0.0820 AC: 2553 AN: 31118

American (AMR) AF: 0.0266 AC: 1184 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 671 AN: 25410

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39186

South Asian (SAS) AF: 0.0166 AC: 1392 AN: 83994

European-Finnish (FIN) AF: 0.0175 AC: 932 AN: 53224

Middle Eastern (MID) AF: 0.0381 AC: 211 AN: 5542

European-Non Finnish (NFE) AF: 0.0425 AC: 43382 AN: 1019848

Other (OTH) AF: 0.0381 AC: 2170 AN: 56922

GnomAD4 genome AF: 0.0460 AC: 6994 AN: 152150 Hom.: 205 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74386

African (AFR) AF: 0.0743 AC: 3083 AN: 41512

American (AMR) AF: 0.0373 AC: 571 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3466

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4822

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2841 AN: 67994

Other (OTH) AF: 0.0474 AC: 100 AN: 2110

Alfa AF: 0.0441 Hom.: 34

Bravo AF: 0.0511

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs35712968; hg19: chr10-100219262;