rs143678537

Variant names:

• chr3-50318367-C-A
• rs143678537
• NM_003773.5:c.1184G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-50318367-C-A
• chr3-50318367-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003773.5(HYAL2):​c.1184G>T​(p.Arg395Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: HYAL2 NM_003773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

Genes affected

HYAL2 (HGNC:5321): (hyaluronidase 2) This gene encodes a weak acid-active hyaluronidase. The encoded protein is similar in structure to other more active hyaluronidases. Hyaluronidases degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan and fragments of hyaluronan are thought to be involved in cell proliferation, migration and differentiation. Although it was previously thought to be a lysosomal hyaluronidase that is active at a pH below 4, the encoded protein is likely a GPI-anchored cell surface protein. This hyaluronidase serves as a receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4002418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL2	NM_003773.5	c.1184G>T	p.Arg395Leu	missense_variant	Exon 4 of 4	ENST00000357750.9	NP_003764.3
HYAL2	NM_033158.5	c.1184G>T	p.Arg395Leu	missense_variant	Exon 5 of 5		NP_149348.2
HYAL2	XM_005265524.3	c.1184G>T	p.Arg395Leu	missense_variant	Exon 5 of 5		XP_005265581.1
HYAL2	XM_005265525.3	c.1184G>T	p.Arg395Leu	missense_variant	Exon 4 of 4		XP_005265582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL2	ENST00000357750.9	c.1184G>T	p.Arg395Leu	missense_variant	Exon 4 of 4	1	NM_003773.5	ENSP00000350387.4
HYAL2	ENST00000395139.7	c.1184G>T	p.Arg395Leu	missense_variant	Exon 4 of 4	1		ENSP00000378571.3
HYAL2	ENST00000447092.5	c.1184G>T	p.Arg395Leu	missense_variant	Exon 3 of 3	1		ENSP00000401853.1
HYAL2	ENST00000442581.1	c.1184G>T	p.Arg395Leu	missense_variant	Exon 5 of 5	2		ENSP00000406657.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461048 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726834

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;D;D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	.;.;.;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M;M;M;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.80	P;P;P;P
Vest4		0.45
MutPred		0.45		Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);
MVP		0.56
MPC		0.68
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs143678537; hg19: chr3-50355798;