8-121622260-C-G

Variant names:

• chr8-121622260-C-G
• rs6651224
• NM_005328.3:c.628-5054G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 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.628-5054G>C		intron	N/A	NP_005319.1	Q92819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS2	ENST00000303924.5	TSL:1 MANE Select	c.628-5054G>C		intron	N/A	ENSP00000306991.4	Q92819

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

African (AFR) AF: 0.190 AC: 7873 AN: 41478

American (AMR) AF: 0.198 AC: 3027 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3466

East Asian (EAS) AF: 0.108 AC: 558 AN: 5176

South Asian (SAS) AF: 0.138 AC: 665 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10576

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14600 AN: 67936

Other (OTH) AF: 0.218 AC: 460 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6651224; hg19: chr8-122634500;