8-121641007-A-G

Variant names:

• chr8-121641007-A-G
• rs1057308
• NM_005328.3:c.-155T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 9 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005328.3. 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
	HAS2	NM_005328.3	MANE Select	c.-155T>C		5_prime_UTR	Exon 1 of 4	NP_005319.1	Q92819
	HAS2-AS1	NR_002835.2		n.824-183A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS2	ENST00000303924.5	TSL:1 MANE Select	c.-155T>C		5_prime_UTR	Exon 1 of 4	ENSP00000306991.4	Q92819
	HAS2-AS1	ENST00000514180.6	TSL:1	n.824-183A>G		intron	N/A
	HAS2-AS1	ENST00000518865.6	TSL:4	n.94-183A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53260 AN: 151404 Hom.: 10496 Cov.: 29

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: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.352 AC: 53336 AN: 151522 Hom.: 10517 Cov.: 29 AF XY: 0.357 AC XY: 26443 AN XY: 74034

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: 78 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17417 AN: 67924

Other (OTH) AF: 0.353 AC: 742 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		1.8
Mutation Taster		=300/0	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: rs1057308; hg19: chr8-122653247;