17-49142166-A-T

Variant names:

• chr17-49142166-A-T
• rs374155308
• NM_001159387.2:c.347A>T

Variant summary

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

The NM_001159387.2(B4GALNT2):​c.347A>T​(p.Gln116Leu) 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. Q116R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: B4GALNT2 NM_001159387.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

B4GALNT2 (HGNC:24136): (beta-1,4-N-acetyl-galactosaminyltransferase 2 (SID blood group)) B4GALNT2 catalyzes the last step in the biosynthesis of the human Sd(a) antigen through the addition of an N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue substituted with an alpha-2,3-linked sialic acid. B4GALNT2 also catalyzes the last step in the biosynthesis of the Cad antigen (Montiel et al., 2003 [PubMed 12678917]).[supplied by OMIM, Mar 2008]

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_001159387.2. 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
	B4GALNT2	NM_001159387.2	MANE Select	c.347A>T	p.Gln116Leu	missense	Exon 3 of 11	NP_001152859.1	Q8NHY0-2
	B4GALNT2	NM_153446.3		c.527A>T	p.Gln176Leu	missense	Exon 3 of 11	NP_703147.2	Q8NHY0-1
	B4GALNT2	NM_001159388.2		c.269A>T	p.Gln90Leu	missense	Exon 3 of 11	NP_001152860.1	Q8NHY0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT2	ENST00000393354.7	TSL:1 MANE Select	c.347A>T	p.Gln116Leu	missense	Exon 3 of 11	ENSP00000377022.3	Q8NHY0-2
	B4GALNT2	ENST00000300404.2	TSL:1	c.527A>T	p.Gln176Leu	missense	Exon 3 of 11	ENSP00000300404.2	Q8NHY0-1
	B4GALNT2	ENST00000954078.1		c.347A>T	p.Gln116Leu	missense	Exon 3 of 12	ENSP00000624137.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.7
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Benign	0.37	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.30		Loss of disorder (P = 0.0337)
MVP		0.72
MPC		0.25
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.22
gMVP		0.65

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: rs374155308; hg19: chr17-47219528;