rs782089963

Variant names:

• chr3-50320483-C-A
• rs782089963
• NM_003773.5:c.7G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-50320483-C-A
• chr3-50320483-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003773.5(HYAL2):​c.7G>T​(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HYAL2 NM_003773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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]

TUSC2 (HGNC:17034): (tumor suppressor 2, mitochondrial calcium regulator) Predicted to be involved in inflammatory response and regulation of mitochondrial membrane potential. Predicted to act upstream of or within several processes, including natural killer cell differentiation; neutrophil-mediated killing of gram-negative bacterium; and regulation of cytokine production. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12948239).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003773.5. 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
	HYAL2	NM_003773.5	MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 2 of 4	NP_003764.3
	HYAL2	NM_033158.5		c.7G>T	p.Ala3Ser	missense	Exon 3 of 5	NP_149348.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL2	ENST00000357750.9	TSL:1 MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 2 of 4	ENSP00000350387.4	Q12891
	HYAL2	ENST00000395139.7	TSL:1	c.7G>T	p.Ala3Ser	missense	Exon 2 of 4	ENSP00000378571.3	Q12891
	HYAL2	ENST00000447092.5	TSL:1	c.7G>T	p.Ala3Ser	missense	Exon 1 of 3	ENSP00000401853.1	Q12891

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382898 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 679888

African (AFR) AF: 0.00 AC: 0 AN: 31204

American (AMR) AF: 0.00 AC: 0 AN: 33912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20794

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38974

South Asian (SAS) AF: 0.00 AC: 0 AN: 73288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4754

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1074954

Other (OTH) AF: 0.00 AC: 0 AN: 56892

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.020
Sift	Uncertain	0.028	D
Sift4G	Benign	0.32	T
Polyphen		0.19	B
Vest4		0.14
MutPred		0.15		Gain of glycosylation at A3 (P = 8e-04)
MVP		0.60
MPC		0.52
ClinPred		0.41	T
GERP RS		3.9
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.40
Mutation Taster		=96/4	polymorphism

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: rs782089963; hg19: chr3-50357914;