rs758824521

Variant names:

• chr3-143120970-C-A
• rs758824521
• NM_004267.5:c.154C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-143120970-C-A
• chr3-143120970-C-G
• chr3-143120970-C-T

Variant summary

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

The NM_004267.5(CHST2):​c.154C>A​(p.Arg52Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,389,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R52G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CHST2 NM_004267.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• Publications: 0 publications found

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]

ENSG00000241679 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST2	NM_004267.5	c.154C>A	p.Arg52Ser	missense_variant	Exon 2 of 2	ENST00000309575.5	NP_004258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST2	ENST00000309575.5	c.154C>A	p.Arg52Ser	missense_variant	Exon 2 of 2	1	NM_004267.5	ENSP00000307911.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389598 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686502

⚠️ 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: 29848

American (AMR) AF: 0.00 AC: 0 AN: 34806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24550

East Asian (EAS) AF: 0.0000286 AC: 1 AN: 34982

South Asian (SAS) AF: 0.00 AC: 0 AN: 77562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4078

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077400

Other (OTH) AF: 0.00 AC: 0 AN: 57476

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), 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
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.97	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.2	N
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.55
MutPred		0.40		Loss of helix (P = 0.0167);
MVP		0.92
MPC		1.1
ClinPred		0.85	D
GERP RS		3.4
Varity_R		0.66
gMVP		0.66
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs758824521; hg19: chr3-142839812;