chr8-121624601-T-G

Variant names:

• chr8-121624601-T-G
• rs6998348
• NM_005328.3:c.627+4113A>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.627+4113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,088 control chromosomes in the GnomAD database, including 7,746 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 0.31 (7746 hom., cov: 32)
• Consequence: HAS2 NM_005328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS2	NM_005328.3	MANE Select	c.627+4113A>C		intron	N/A	NP_005319.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS2	ENST00000303924.5	TSL:1 MANE Select	c.627+4113A>C		intron	N/A	ENSP00000306991.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46863 AN: 151970 Hom.: 7721 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.309 AC: 46933 AN: 152088 Hom.: 7746 Cov.: 32 AF XY: 0.303 AC XY: 22530 AN XY: 74366

African (AFR) AF: 0.418 AC: 17333 AN: 41474

American (AMR) AF: 0.269 AC: 4118 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1178 AN: 3470

East Asian (EAS) AF: 0.119 AC: 612 AN: 5162

South Asian (SAS) AF: 0.199 AC: 961 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2448 AN: 10596

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19216 AN: 67956

Other (OTH) AF: 0.315 AC: 667 AN: 2116

Alfa AF: 0.303 Hom.: 1253

Bravo AF: 0.320

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.087
DANN	Benign	0.48
PhyloP100		-2.8
Mutation Taster		=100/0	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: rs6998348; hg19: chr8-122636841;