chr17-76572644-T-G

Variant names:

• chr17-76572644-T-G
• rs759934050
• NM_006456.3:c.662A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006456.3(ST6GALNAC2):​c.662A>C​(p.Gln221Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q221R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GALNAC2 NM_006456.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006456.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC2	NM_006456.3	MANE Select	c.662A>C	p.Gln221Pro	missense	Exon 5 of 9	NP_006447.2	Q9UJ37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC2	ENST00000225276.10	TSL:1 MANE Select	c.662A>C	p.Gln221Pro	missense	Exon 5 of 9	ENSP00000225276.4	Q9UJ37
	ST6GALNAC2	ENST00000909969.1		c.662A>C	p.Gln221Pro	missense	Exon 5 of 9	ENSP00000580028.1
	ST6GALNAC2	ENST00000943099.1		c.812A>C	p.Gln271Pro	missense	Exon 5 of 9	ENSP00000613158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.8
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.27
Sift	Benign	0.095	T
Sift4G	Benign	0.21	T
Polyphen		0.95	P
Vest4		0.71
MutPred		0.59		Gain of catalytic residue at P220 (P = 0.0143)
MVP		0.32
MPC		0.76
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.85
gMVP		0.82

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

Other links and lift over

dbSNP: rs759934050; hg19: chr17-74568726;