3-143121009-C-G

Position:

• chr3-143121009-C-G

Variant summary

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

The NM_004267.5(CHST2):​c.193C>G​(p.Leu65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2.55

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.193C>G	p.Leu65Val	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.193C>G	p.Leu65Val	missense_variant	2/2	1	NM_004267.5	ENSP00000307911	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389248 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685972

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

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

Jun 21, 2023

The c.193C>G (p.L65V) 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 193, causing the leucine (L) at amino acid position 65 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.55	N
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.20
MutPred		0.25		Gain of catalytic residue at L65 (P = 0.0028);
MVP		0.96
MPC		1.2
ClinPred		0.60	D
GERP RS		3.0
Varity_R		0.60
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-142839851;