NM_152490.5:c.755T>G

Variant names:

• chr1-235470857-A-C
• rs367543073
• NM_152490.5:c.755T>G

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 rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.755T>G	p.Val252Gly	missense_variant	Exon 6 of 12	ENST00000366600.8	NP_689703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.755T>G	p.Val252Gly	missense_variant	Exon 6 of 12	1	NM_152490.5	ENSP00000355559.3

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

Mar 07, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 27, 2013

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Other:1

-

Leiden Muscular Dystrophy pages (B3GALNT2)

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

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;.
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;