17-76570592-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006456.3(ST6GALNAC2):c.746T>C(p.Val249Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GALNAC2 NM_006456.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.10

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]

(HGNC:):

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GALNAC2	NM_006456.3	c.746T>C	p.Val249Ala	missense_variant	6/9	ENST00000225276.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GALNAC2	ENST00000225276.10	c.746T>C	p.Val249Ala	missense_variant	6/9	1	NM_006456.3	P1
	ENST00000588104.1	n.801A>G		non_coding_transcript_exon_variant	1/1
SNHG16	ENST00000701062.1	n.194+9194A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 07, 2022

The c.746T>C (p.V249A) alteration is located in exon 6 (coding exon 6) of the ST6GALNAC2 gene. This alteration results from a T to C substitution at nucleotide position 746, causing the valine (V) at amino acid position 249 to be replaced by an alanine (A). 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	0.56
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.9	D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.0060	D;.
Polyphen		0.95	P;.
Vest4		0.74
MutPred		0.65		Gain of helix (P = 0.062);.;
MVP		0.17
MPC		0.74
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.58
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-74566674;