15-92464096-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006011.4(ST8SIA2):c.843-4C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ST8SIA2 NM_006011.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008436
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

Genes affected

ST8SIA2 (HGNC:10870): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-92464096-C-A is Benign according to our data. Variant chr15-92464096-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 737670.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA2	NM_006011.4	c.843-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000268164.8
ST8SIA2	NM_001330416.2	c.780-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ST8SIA2	XM_017022642.2	c.906-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.843-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006011.4	P1
ST8SIA2	ENST00000539113.5	c.780-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
ST8SIA2	ENST00000555434.1	c.714-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 36248 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000115

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00828 AC: 5780 AN: 698124 Hom.: 0 Cov.: 31 AF XY: 0.00793 AC XY: 2753 AN XY: 347338

Gnomad4 AFR exome AF: 0.00954

Gnomad4 AMR exome AF: 0.00467

Gnomad4 ASJ exome AF: 0.00517

Gnomad4 EAS exome AF: 0.00708

Gnomad4 SAS exome AF: 0.00331

Gnomad4 FIN exome AF: 0.00434

Gnomad4 NFE exome AF: 0.00892

Gnomad4 OTH exome AF: 0.00717

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000193 AC: 7 AN: 36270 Hom.: 0 Cov.: 0 AF XY: 0.000234 AC XY: 4 AN XY: 17082

Gnomad4 AFR AF: 0.000112

Gnomad4 AMR AF: 0.000615

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.000115

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.53
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.092
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: rs1375015257; hg19: chr15-93007326;