2-219539658-C-T

Variant names:

• chr2-219539658-C-T
• rs757492342
• NM_024536.6:c.2053G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024536.6(CHPF):​c.2053G>A​(p.Val685Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V685L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101613164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHPF	NM_024536.6	c.2053G>A	p.Val685Met	missense_variant	Exon 4 of 4	ENST00000243776.11	NP_078812.3
CHPF	NM_001195731.2	c.1567G>A	p.Val523Met	missense_variant	Exon 4 of 4		NP_001182660.2
CHPF	XM_011511838.4	c.1180G>A	p.Val394Met	missense_variant	Exon 3 of 3		XP_011510140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHPF	ENST00000243776.11	c.2053G>A	p.Val685Met	missense_variant	Exon 4 of 4	1	NM_024536.6	ENSP00000243776.6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152236 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 247784 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134572

Gnomad AFR exome AF: 0.0000635

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1461188 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726916

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152352 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74508

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.81
DEOGEN2	Benign	0.072	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.093
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.023	B;.
Vest4		0.13
MutPred		0.34		Gain of disorder (P = 0.055);.;
MVP		0.32
MPC		0.26
ClinPred		0.045	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs757492342; hg19: chr2-220404380;