1-235504223-C-G

Variant names:

• chr1-235504223-C-G
• rs986453979
• NM_152490.5:c.30G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_152490.5(B3GALNT2):​c.30G>C​(p.Pro10Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,322,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.831 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 12	ENST00000366600.8	NP_689703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 12	1	NM_152490.5	ENSP00000355559.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1322576 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 652196

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26568

American (AMR) AF: 0.00 AC: 0 AN: 27554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23084

East Asian (EAS) AF: 0.00 AC: 0 AN: 27968

South Asian (SAS) AF: 0.00 AC: 0 AN: 73870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4038

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051954

Other (OTH) AF: 0.0000183 AC: 1 AN: 54788

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		0.83
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs986453979; hg19: chr1-235667523;