3-50318387-A-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_003773.5(HYAL2):āc.1164T>Cā(p.His388His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,613,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.0016 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
HYAL2
NM_003773.5 synonymous
NM_003773.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.55
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 3-50318387-A-G is Benign according to our data. Variant chr3-50318387-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052597.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=1.55 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (246/152394) while in subpopulation AFR AF= 0.0057 (237/41598). AF 95% confidence interval is 0.0051. There are 0 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| HYAL2 | NM_003773.5 | c.1164T>C | p.His388His | synonymous_variant | 4/4 | ENST00000357750.9 | NP_003764.3 | |
| HYAL2 | NM_033158.5 | c.1164T>C | p.His388His | synonymous_variant | 5/5 | NP_149348.2 | ||
| HYAL2 | XM_005265524.3 | c.1164T>C | p.His388His | synonymous_variant | 5/5 | XP_005265581.1 | ||
| HYAL2 | XM_005265525.3 | c.1164T>C | p.His388His | synonymous_variant | 4/4 | XP_005265582.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HYAL2 | ENST00000357750.9 | c.1164T>C | p.His388His | synonymous_variant | 4/4 | 1 | NM_003773.5 | ENSP00000350387.4 | ||
| HYAL2 | ENST00000395139.7 | c.1164T>C | p.His388His | synonymous_variant | 4/4 | 1 | ENSP00000378571.3 | |||
| HYAL2 | ENST00000447092.5 | c.1164T>C | p.His388His | synonymous_variant | 3/3 | 1 | ENSP00000401853.1 | |||
| HYAL2 | ENST00000442581.1 | c.1164T>C | p.His388His | synonymous_variant | 5/5 | 2 | ENSP00000406657.1 |
Frequencies
GnomAD3 genomes 0.00162 AC: 246AN: 152276Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000411 AC: 103AN: 250778Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135810
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GnomAD4 exome AF: 0.000153 AC: 224AN: 1460974Hom.: 0 Cov.: 31 AF XY: 0.000142 AC XY: 103AN XY: 726796
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GnomAD4 genome 0.00161 AC: 246AN: 152394Hom.: 0 Cov.: 32 AF XY: 0.00150 AC XY: 112AN XY: 74530
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HYAL2-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at