chr3-143120970-C-G

Position:

• chr3-143120970-C-G

Variant summary

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

The NM_004267.5(CHST2):​c.154C>G​(p.Arg52Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST2 NM_004267.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48

Genes affected

CHST2 (HGNC:1970): (carbohydrate sulfotransferase 2) This locus encodes a sulfotransferase protein. The encoded enzyme catalyzes the sulfation of a nonreducing N-acetylglucosamine residue, and may play a role in biosynthesis of 6-sulfosialyl Lewis X antigen. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST2	NM_004267.5	c.154C>G	p.Arg52Gly	missense_variant	2/2	ENST00000309575.5	NP_004258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST2	ENST00000309575.5	c.154C>G	p.Arg52Gly	missense_variant	2/2	1	NM_004267.5	ENSP00000307911.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389600 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686502

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000877 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.154C>G (p.R52G) alteration is located in exon 2 (coding exon 1) of the CHST2 gene. This alteration results from a C to G substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.7	N
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.42		Loss of helix (P = 0.0167);
MVP		0.96
MPC		1.3
ClinPred		0.83	D
GERP RS		3.4
Varity_R		0.61
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs758824521; hg19: chr3-142839812;