8-121622260-C-G

Position:

• chr8-121622260-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005328.3(HAS2):​c.628-5054G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,032 control chromosomes in the GnomAD database, including 3,080 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 0.20 (3080 hom., cov: 31)
• Consequence: HAS2 NM_005328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAS2	NM_005328.3	c.628-5054G>C		intron_variant		ENST00000303924.5	NP_005319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAS2	ENST00000303924.5	c.628-5054G>C		intron_variant		1	NM_005328.3	ENSP00000306991.4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30043 AN: 151914 Hom.: 3076 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.198 AC: 30067 AN: 152032 Hom.: 3080 Cov.: 31 AF XY: 0.193 AC XY: 14344 AN XY: 74320

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.218

Alfa AF: 0.0936 Hom.: 124

Bravo AF: 0.204

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6651224; hg19: chr8-122634500;