17-49156590-C-A

Variant names:

• chr17-49156590-C-A
• rs560373909
• NM_001159387.2:c.485C>A

Variant summary

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

The NM_001159387.2(B4GALNT2):​c.485C>A​(p.Ala162Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: B4GALNT2 NM_001159387.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=0.21199319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT2	NM_001159387.2	c.485C>A	p.Ala162Asp	missense_variant	Exon 5 of 11	ENST00000393354.7	NP_001152859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT2	ENST00000393354.7	c.485C>A	p.Ala162Asp	missense_variant	Exon 5 of 11	1	NM_001159387.2	ENSP00000377022.3
B4GALNT2	ENST00000300404.2	c.665C>A	p.Ala222Asp	missense_variant	Exon 5 of 11	1		ENSP00000300404.2
B4GALNT2	ENST00000504681.5	c.407C>A	p.Ala136Asp	missense_variant	Exon 5 of 11	2		ENSP00000425510.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250798 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135568

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727026

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.9
DANN	Benign	0.97
DEOGEN2	Benign	0.068	.;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.59, 0.95	.;P;P
Vest4		0.41
MutPred		0.30		.;.;Gain of disorder (P = 0.0605);
MVP		0.58
MPC		0.24
ClinPred		0.35	T
GERP RS		2.7
Varity_R		0.097
gMVP		0.56

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: rs560373909; hg19: chr17-47233952;