17-76567466-T-C

Position:

• chr17-76567466-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006456.3(ST6GALNAC2):​c.944A>G​(p.His315Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000021 (0 hom.)
• Consequence: ST6GALNAC2 NM_006456.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.24

Genes affected

ST6GALNAC2 (HGNC:10867): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2) ST6GALNAC2 belongs to a family of sialyltransferases that add sialic acids to the nonreducing ends of glycoconjugates. At the cell surface, these modifications have roles in cell-cell and cell-substrate interactions, bacterial adhesion, and protein targeting (Samyn-Petit et al., 2000 [PubMed 10742600]).[supplied by OMIM, Mar 2008]

ENSG00000284526 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC2	NM_006456.3	c.944A>G	p.His315Arg	missense_variant	8/9	ENST00000225276.10	NP_006447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC2	ENST00000225276.10	c.944A>G	p.His315Arg	missense_variant	8/9	1	NM_006456.3	ENSP00000225276.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461204 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726916

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.944A>G (p.H315R) alteration is located in exon 8 (coding exon 8) of the ST6GALNAC2 gene. This alteration results from a A to G substitution at nucleotide position 944, causing the histidine (H) at amino acid position 315 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.8	D;.
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0080	D;.
Polyphen		1.0	D;.
Vest4		0.95
MutPred		0.76		Gain of relative solvent accessibility (P = 0.1259);.;
MVP		0.44
MPC		0.77
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.95
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74563548;