2-219539619-C-T

Variant names:

• chr2-219539619-C-T
• rs143750392
• NM_024536.6:c.2092G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024536.6(CHPF):​c.2092G>A​(p.Glu698Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,613,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E698Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 8 publications found

Genes affected

CHPF (HGNC:24291): (chondroitin polymerizing factor) Enables N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity and glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity. Involved in chondroitin sulfate biosynthetic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047728747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024536.6. 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
	CHPF	NM_024536.6	MANE Select	c.2092G>A	p.Glu698Lys	missense	Exon 4 of 4	NP_078812.3
	CHPF	NM_001195731.2		c.1606G>A	p.Glu536Lys	missense	Exon 4 of 4	NP_001182660.2	Q8IZ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHPF	ENST00000243776.11	TSL:1 MANE Select	c.2092G>A	p.Glu698Lys	missense	Exon 4 of 4	ENSP00000243776.6	Q8IZ52-1
	CHPF	ENST00000691864.1		c.2068G>A	p.Glu690Lys	missense	Exon 4 of 4	ENSP00000509104.1	A0A8I5QJC8
	CHPF	ENST00000919936.1		c.2014G>A	p.Glu672Lys	missense	Exon 4 of 4	ENSP00000589995.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152266 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000164 AC: 41 AN: 249852 AF XY: 0.000192

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000216 AC: 315 AN: 1461554 Hom.: 1 Cov.: 30 AF XY: 0.000249 AC XY: 181 AN XY: 727118

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.000268 AC: 12 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000231 AC: 257 AN: 1111934

Other (OTH) AF: 0.000265 AC: 16 AN: 60386

GnomAD4 genome AF: 0.000249 AC: 38 AN: 152384 Hom.: 0 Cov.: 34 AF XY: 0.000268 AC XY: 20 AN XY: 74518

African (AFR) AF: 0.000144 AC: 6 AN: 41600

American (AMR) AF: 0.00131 AC: 20 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000183 Hom.: 0

Bravo AF: 0.000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0016
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.088
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.15	B
Vest4		0.32
MVP		0.44
MPC		0.43
ClinPred		0.017	T
GERP RS		3.6
Varity_R		0.076
gMVP		0.65
Mutation Taster		=90/10	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: rs143750392; hg19: chr2-220404341; COSMIC: COSV99704670; COSMIC: COSV99704670;