rs114779238

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138477.4(CDAN1):c.2836C>T(p.Arg946Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,613,816 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R946Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 33 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.33

Publications

9 publications found

Variant links:

Genes affected

CDAN1 (HGNC:1713): (codanin 1) This gene encodes a protein that appears to play a role in nuclear envelope integrity, possibly related to microtubule attachments. Mutations in this gene cause congenital dyserythropoietic anemia type I, a disease resulting in morphological and functional abnormalities of erythropoiesis. [provided by RefSeq, Jul 2009]

CDAN1 Gene-Disease associations (from GenCC):

anemia, congenital dyserythropoietic, type 1a
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital dyserythropoietic anemia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

CDAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008565098).

BP6

Variant 15-42728236-G-A is Benign according to our data. Variant chr15-42728236-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1775/152262) while in subpopulation AFR AF = 0.0382 (1586/41540). AF 95% confidence interval is 0.0366. There are 26 homozygotes in GnomAd4. There are 872 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.2836C>T	p.Arg946Trp	missense_variant	Exon 21 of 28	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDAN1	ENST00000356231.4 link	c.2836C>T	p.Arg946Trp	missense_variant	Exon 21 of 28	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000562465.5 link	n.829C>T		non_coding_transcript_exon_variant	Exon 8 of 15	1		ENSP00000454246.1	H3BM60
CDAN1	ENST00000643434.1 link	n.*2014C>T		non_coding_transcript_exon_variant	Exon 19 of 25			ENSP00000494699.1	A0A2R8Y5C2
CDAN1	ENST00000643434.1 link	n.*2014C>T		3_prime_UTR_variant	Exon 19 of 25			ENSP00000494699.1	A0A2R8Y5C2

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1768

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00398

AC:

999

AN:

250836

AF XY:

0.00324

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00162

AC:

2366

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1115

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.0375

AC:

1256

AN:

33476

American (AMR)

AF:

0.00360

AC:

161

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00501

AC:

131

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00122

AC:

105

AN:

86256

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000426

AC:

474

AN:

1111960

Other (OTH)

AF:

0.00358

AC:

216

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

157

314

470

627

784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0117

AC:

1775

AN:

152262

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

872

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0382

AC:

1586

AN:

41540

American (AMR)

AF:

0.00627

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68026

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

174

260

347

434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00422

Hom.:

Bravo

AF:

0.0137

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0379

AC:

167

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00455

AC:

552

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 24, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CDAN1: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital dyserythropoietic anemia, type I

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Anemia, congenital dyserythropoietic, type 1a

Benign:1

May 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0086

MetaSVM

Uncertain

-0.020

MutationAssessor

Uncertain

2.1

PhyloP100

2.3

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.61

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.69

MVP

0.47

MPC

0.34

ClinPred

0.035

GERP RS

5.2

Varity_R

0.39

gMVP

0.50

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over