17-49133051-G-C

Variant names:

• chr17-49133051-G-C
• rs780338935
• ENST00000300404.2:c.26G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153446.3(B4GALNT2):​c.26G>C​(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,347,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: B4GALNT2 NM_153446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110979706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT2	NM_001159387.2	c.14+245G>C		intron_variant	Intron 1 of 10	ENST00000393354.7	NP_001152859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT2	ENST00000300404.2	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 11	1		ENSP00000300404.2
B4GALNT2	ENST00000393354.7	c.14+245G>C		intron_variant	Intron 1 of 10	1	NM_001159387.2	ENSP00000377022.3
B4GALNT2	ENST00000504681.5	c.-65+541G>C		intron_variant	Intron 1 of 10	2		ENSP00000425510.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000190 AC: 3 AN: 157904 Hom.: 0 AF XY: 0.0000113 AC XY: 1 AN XY: 88166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1347252 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 664784

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000282

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.8
DANN	Benign	0.93
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.029
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.18
MutPred		0.40		Gain of sheet (P = 0.039);
MVP		0.39
MPC		0.56
ClinPred		0.16	T
GERP RS		1.6
Varity_R		0.11
gMVP		0.063

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

LitVar

Other links and lift over

dbSNP: rs780338935; hg19: chr17-47210413;