Genetic Variant CHRDL2:p.Arg301His (chr11-74703349-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001278473.3(CHRDL2):c.902G>A(p.Arg301His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CHRDL2
NM_001278473.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.277

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039506644).

BP6

Variant 11-74703349-C-T is Benign according to our data. Variant chr11-74703349-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3144575.Status of the report is criteria_provided_single_submitter, 1 stars.

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.902G>A	p.Arg301His	missense	Exon 8 of 11	NP_001265402.1	Q6WN34-1
CHRDL2	NM_015424.6		c.902G>A	p.Arg301His	missense	Exon 8 of 12	NP_056239.3
CHRDL2	NM_001304390.2		c.842G>A	p.Arg281His	missense	Exon 7 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.902G>A	p.Arg301His	missense	Exon 8 of 11	ENSP00000365510.3	Q6WN34-1
CHRDL2	ENST00000263671.9	TSL:1	c.902G>A	p.Arg301His	missense	Exon 8 of 12	ENSP00000263671.5	Q6WN34-2
CHRDL2	ENST00000528789.1	TSL:1	c.752-382G>A		intron	N/A	ENSP00000431380.1	Q6WN33

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

250402

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460352

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726404

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33434

American (AMR)

AF:

0.0000449

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111294

Other (OTH)

AF:

0.0000829

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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

AF:

0.000112

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41550

American (AMR)

AF:

0.000719

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.6

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.14

M_CAP

Benign

0.0077

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.44

PhyloP100

0.28

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.55

REVEL

Benign

0.13

Sift

Benign

0.39

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.17

MVP

0.33

MPC

0.30

ClinPred

0.029

GERP RS

-11

Varity_R

0.020

gMVP

0.17

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over