3-50320498-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003773.5(HYAL2):c.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,522,490 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 11 hom. )

Consequence

HYAL2
NM_003773.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

Publications

3 publications found

Variant links:

Genes affected

HYAL2 (HGNC:5321): (hyaluronidase 2) This gene encodes a weak acid-active hyaluronidase. The encoded protein is similar in structure to other more active hyaluronidases. Hyaluronidases degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan and fragments of hyaluronan are thought to be involved in cell proliferation, migration and differentiation. Although it was previously thought to be a lysosomal hyaluronidase that is active at a pH below 4, the encoded protein is likely a GPI-anchored cell surface protein. This hyaluronidase serves as a receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR.[provided by RefSeq, Mar 2010]

HYAL2 links:

TUSC2 (HGNC:17034): (tumor suppressor 2, mitochondrial calcium regulator) Predicted to be involved in inflammatory response and regulation of mitochondrial membrane potential. Predicted to act upstream of or within several processes, including natural killer cell differentiation; neutrophil-mediated killing of gram-negative bacterium; and regulation of cytokine production. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TUSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-50320498-C-T is Benign according to our data. Variant chr3-50320498-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1691221.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00784 (1195/152362) while in subpopulation AFR AF = 0.0276 (1146/41596). AF 95% confidence interval is 0.0262. There are 16 homozygotes in GnomAd4. There are 542 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003773.5. 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
	HYAL2	NM_003773.5	MANE Select	c.-9G>A		5_prime_UTR	Exon 2 of 4	NP_003764.3
	HYAL2	NM_033158.5		c.-9G>A		5_prime_UTR	Exon 3 of 5	NP_149348.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYAL2	ENST00000357750.9	TSL:1 MANE Select	c.-9G>A	5_prime_UTR	Exon 2 of 4	ENSP00000350387.4	Q12891
HYAL2	ENST00000395139.7	TSL:1	c.-9G>A	5_prime_UTR	Exon 2 of 4	ENSP00000378571.3	Q12891
HYAL2	ENST00000447092.5	TSL:1	c.-9G>A	5_prime_UTR	Exon 1 of 3	ENSP00000401853.1	Q12891

Frequencies

GnomAD3 genomes

AF:

0.00768

AC:

1169

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00276

AC:

451

AN:

163132

AF XY:

0.00214

show subpopulations

Gnomad AFR exome

AF:

0.0312

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.000825

AC:

1131

AN:

1370128

Hom.:

Cov.:

AF XY:

0.000733

AC XY:

493

AN XY:

672624

show subpopulations

African (AFR)

AF:

0.0280

AC:

863

AN:

30772

American (AMR)

AF:

0.00188

AC:

AN:

31462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20286

East Asian (EAS)

AF:

0.00

AC:

AN:

38752

South Asian (SAS)

AF:

0.000335

AC:

AN:

71690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46048

Middle Eastern (MID)

AF:

0.00273

AC:

AN:

4388

European-Non Finnish (NFE)

AF:

0.0000392

AC:

AN:

1070320

Other (OTH)

AF:

0.00232

AC:

131

AN:

56410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00784

AC:

1195

AN:

152362

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

542

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0276

AC:

1146

AN:

41596

American (AMR)

AF:

0.00203

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00490

Hom.:

Bravo

AF:

0.00931

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.2

PromoterAI

0.00020

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over