Genetic Variant NM_005328.3:c.-155T>C (chr8-121641007-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005328.3(HAS2):c.-155T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,522 control chromosomes in the GnomAD database, including 10,517 homozygotes. 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: 𝑓 0.35 ( 10517 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HAS2
NM_005328.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

9 publications found

Variant links:

Genes affected

HAS2 (HGNC:4819): (hyaluronan synthase 2) Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS2 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1. [provided by RefSeq, Jul 2008]

HAS2 links:

HAS2-AS1 (HGNC:34340): (HAS2 antisense RNA 1)

HAS2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAS2	NM_005328.3 link	c.-155T>C		5_prime_UTR_variant	Exon 1 of 4	ENST00000303924.5	NP_005319.1	Q92819
HAS2-AS1	NR_002835.2 link	n.824-183A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAS2	ENST00000303924.5 link	c.-155T>C		5_prime_UTR_variant	Exon 1 of 4	1	NM_005328.3	ENSP00000306991.4		Q92819

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53260

AN:

151404

Hom.:

10496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.352

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.352

AC:

53336

AN:

151522

Hom.:

10517

Cov.:

AF XY:

0.357

AC XY:

26443

AN XY:

74034

show subpopulations

African (AFR)

AF:

0.465

AC:

19191

AN:

41260

American (AMR)

AF:

0.404

AC:

6143

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

890

AN:

3466

East Asian (EAS)

AF:

0.730

AC:

3751

AN:

5138

South Asian (SAS)

AF:

0.316

AC:

1511

AN:

4778

European-Finnish (FIN)

AF:

0.328

AC:

3420

AN:

10428

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17417

AN:

67924

Other (OTH)

AF:

0.353

AC:

742

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.289

Hom.:

11265

Bravo

AF:

0.366

Asia WGS

AF:

0.533

AC:

1852

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.8

Mutation Taster

=300/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over