Genetic Variant CHST2:p.Gly134Arg (chr3-143121216-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004267.5(CHST2):c.400G>A(p.Gly134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHST2
NM_004267.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.225

Publications

1 publications found

Variant links:

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]

CHST2 links:

ENSG00000241679 (HGNC:):

ENSG00000241679 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2125268).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004267.5. 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
	CHST2	NM_004267.5	MANE Select	c.400G>A	p.Gly134Arg	missense	Exon 2 of 2	NP_004258.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST2	ENST00000309575.5	TSL:1 MANE Select	c.400G>A	p.Gly134Arg	missense	Exon 2 of 2	ENSP00000307911.3	Q9Y4C5-1
ENSG00000241679	ENST00000840528.1		n.361-30908G>A		intron	N/A
ENSG00000241679	ENST00000840529.1		n.376-10502G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1418940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703248

show subpopulations

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

African (AFR)

AF:

0.0000614

AC:

AN:

32598

American (AMR)

AF:

0.00

AC:

AN:

39126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24382

East Asian (EAS)

AF:

0.00

AC:

AN:

38678

South Asian (SAS)

AF:

0.00

AC:

AN:

81490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5390

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095042

Other (OTH)

AF:

0.00

AC:

AN:

58704

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

PhyloP100

0.23

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.37

REVEL

Benign

0.20

Sift

Benign

0.12

Sift4G

Uncertain

0.042

Polyphen

0.056

Vest4

0.15

MutPred

0.38

Gain of methylation at G134 (P = 0.0038)

MVP

0.82

MPC

1.2

ClinPred

0.20

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.075

gMVP

0.45

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over