1-86915095-TCGC-GAA

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_012262.4(HS2ST1):c.59_62delinsGAA(p.Phe20Ter) variant causes a stop gained, frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HS2ST1 NM_012262.4 stop_gained, frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.89

Genes affected

HS2ST1 (HGNC:5193): (heparan sulfate 2-O-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-86915095-TCGC-GAA is Pathogenic according to our data. Variant chr1-86915095-TCGC-GAA is described in ClinVar as [Pathogenic]. Clinvar id is 997413.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS2ST1	NM_012262.4	c.59_62delinsGAA	p.Phe20Ter	stop_gained, frameshift_variant	1/7	ENST00000370550.10
HS2ST1	NM_001134492.2	c.59_62delinsGAA	p.Phe20Ter	stop_gained, frameshift_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS2ST1	ENST00000370550.10	c.59_62delinsGAA	p.Phe20Ter	stop_gained, frameshift_variant	1/7	1	NM_012262.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurofacioskeletal syndrome with or without renal agenesis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 18, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1660112720; hg19: chr1-87380778;