rs781198538

Variant names:

• chr1-235480077-C-G
• rs781198538
• NM_152490.5:c.628G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-235480077-C-G
• chr1-235480077-C-T

Variant summary

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

The NM_152490.5(B3GALNT2):​c.628G>C​(p.Val210Leu) variant causes a missense change. 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. V210M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: B3GALNT2 NM_152490.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

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]

B3GALNT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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_152490.5. 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
	B3GALNT2	NM_152490.5	MANE Select	c.628G>C	p.Val210Leu	missense	Exon 5 of 12	NP_689703.1	Q8NCR0-1
	B3GALNT2	NM_001277155.3		c.751G>C	p.Val251Leu	missense	Exon 6 of 8	NP_001264084.1	Q8NCR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.628G>C	p.Val210Leu	missense	Exon 5 of 12	ENSP00000355559.3	Q8NCR0-1
	B3GALNT2	ENST00000313984.3	TSL:1	c.751G>C	p.Val251Leu	missense	Exon 6 of 8	ENSP00000315678.3	Q8NCR0-2
	B3GALNT2	ENST00000954792.1		c.751G>C	p.Val251Leu	missense	Exon 6 of 13	ENSP00000624851.1

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	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.29
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.31		Loss of sheet (P = 0.0817)
MVP		0.77
MPC		0.64
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.67
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs781198538; hg19: chr1-235643393;