rs367543073

chr1-235470857-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1 PM2 PP5 BP4

The NM_152490.5(B3GALNT2):c.755T>G(p.Val252Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. V252V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALNT2 NM_152490.5 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 6.73

Genes affected

B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_152490.5
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-235470857-A-C is Pathogenic according to our data. Variant chr1-235470857-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 41937.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-235470857-A-C is described in UniProt as null. Variant chr1-235470857-A-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.2792105).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALNT2	NM_152490.5	c.755T>G	p.Val252Gly	missense_variant	6/12	ENST00000366600.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.755T>G	p.Val252Gly	missense_variant	6/12	1	NM_152490.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 Pathogenic:2

Likely pathogenic, no assertion criteria provided	literature only	ClinVar Staff, National Center for Biotechnology Information (NCBI)	Jun 27, 2013	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 07, 2013	- -

not provided Other:1

not provided, no classification provided

literature only

Leiden Muscular Dystrophy pages (B3GALNT2)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	0.042
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.011	D;.
Sift4G	Uncertain	0.018	D;D
Polyphen		0.24	B;D
Vest4		0.53
MutPred		0.56		Loss of stability (P = 6e-04);.;
MVP		0.68
MPC		0.59
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.43
gMVP		0.86

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: rs367543073; hg19: chr1-235634171;