Genetic Variant CHRDL2:p.Glu357Gln (chr11-74702845-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001278473.3(CHRDL2):c.1069G>C(p.Glu357Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 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. E357K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHRDL2
NM_001278473.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.11

Publications

1 publications found

Variant links:

Genes affected

CHRDL2 (HGNC:24168): (chordin like 2) This gene encodes a member of the chordin family of proteins. Chordin family members are secreted proteins that share a cysteine-rich pro-collagen repeat domain and associate with members of the transforming growth factor beta superfamily. In vitro assays demonstrate a direct interaction between the encoded protein and human activin A. This gene is expressed in many tissues including osteoblasts, where it is differentially expressed during differentiation. In addition, its expression is upregulated in human osteoarthritic joint cartilage, suggesting a role in adult cartilage regeneration. [provided by RefSeq, Jan 2015]

CHRDL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRDL2	NM_001278473.3	MANE Select	c.1069G>C	p.Glu357Gln	missense	Exon 9 of 11	NP_001265402.1	Q6WN34-1
CHRDL2	NM_015424.6		c.1069G>C	p.Glu357Gln	missense	Exon 9 of 12	NP_056239.3
CHRDL2	NM_001304390.2		c.1009G>C	p.Glu337Gln	missense	Exon 8 of 11	NP_001291319.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRDL2	ENST00000376332.8	TSL:1 MANE Select	c.1069G>C	p.Glu357Gln	missense	Exon 9 of 11	ENSP00000365510.3	Q6WN34-1
CHRDL2	ENST00000263671.9	TSL:1	c.1069G>C	p.Glu357Gln	missense	Exon 9 of 12	ENSP00000263671.5	Q6WN34-2
CHRDL2	ENST00000528789.1	TSL:1	c.874G>C	p.Glu292Gln	missense	Exon 8 of 8	ENSP00000431380.1	Q6WN33

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

0.0093

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.2

PhyloP100

5.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.53

MutPred

0.62

Loss of disorder (P = 0.1629)

MVP

0.86

MPC

0.87

ClinPred

0.96

GERP RS

5.1

Varity_R

0.44

gMVP

0.66

Mutation Taster

=88/12

polymorphism

(source)

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

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