rs8023524

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138477.4(CDAN1):c.2671C>T(p.Arg891Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,806 control chromosomes in the GnomAD database, including 39,195 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R891H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.25 ( 6050 hom., cov: 32)

Exomes 𝑓: 0.20 ( 33145 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.967

Publications

35 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=0.0032268167).

BP6

Variant 15-42728785-G-A is Benign according to our data. Variant chr15-42728785-G-A is described in ClinVar as Benign. ClinVar VariationId is 21749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.2671C>T	p.Arg891Cys	missense	Exon 20 of 28	NP_612486.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.2671C>T	p.Arg891Cys	missense	Exon 20 of 28	ENSP00000348564.3
CDAN1	ENST00000562465.5	TSL:1	n.664C>T		non_coding_transcript_exon	Exon 7 of 15	ENSP00000454246.1
CDAN1	ENST00000643434.1		n.*1849C>T		non_coding_transcript_exon	Exon 18 of 25	ENSP00000494699.1

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38742

AN:

151990

Hom.:

6043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.0625

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.208

AC:

52115

AN:

251126

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.0958

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.0635

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.202

AC:

295429

AN:

1461698

Hom.:

33145

Cov.:

AF XY:

0.207

AC XY:

150275

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.441

AC:

14754

AN:

33480

American (AMR)

AF:

0.102

AC:

4547

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6706

AN:

26136

East Asian (EAS)

AF:

0.0809

AC:

3210

AN:

39696

South Asian (SAS)

AF:

0.353

AC:

30455

AN:

86250

European-Finnish (FIN)

AF:

0.233

AC:

12460

AN:

53410

Middle Eastern (MID)

AF:

0.234

AC:

1347

AN:

5768

European-Non Finnish (NFE)

AF:

0.188

AC:

208951

AN:

1111868

Other (OTH)

AF:

0.215

AC:

12999

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13870

27739

41609

55478

69348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7526

15052

22578

30104

37630

<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:

0.255

AC:

38778

AN:

152108

Hom.:

6050

Cov.:

AF XY:

0.255

AC XY:

18945

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.431

AC:

17872

AN:

41462

American (AMR)

AF:

0.141

AC:

2161

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3470

East Asian (EAS)

AF:

0.0629

AC:

325

AN:

5168

South Asian (SAS)

AF:

0.340

AC:

1640

AN:

4824

European-Finnish (FIN)

AF:

0.232

AC:

2451

AN:

10586

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12806

AN:

67992

Other (OTH)

AF:

0.236

AC:

500

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1367

2735

4102

5470

6837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.201

Hom.:

14634

Bravo

AF:

0.252

TwinsUK

AF:

0.184

AC:

684

ALSPAC

AF:

0.182

AC:

702

ESP6500AA

AF:

0.428

AC:

1886

ESP6500EA

AF:

0.188

AC:

1620

ExAC

AF:

0.215

AC:

26159

Asia WGS

AF:

0.210

AC:

731

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.188

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Anemia, congenital dyserythropoietic, type 1a (1)

Congenital dyserythropoietic anemia, type I (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

0.97

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.25

Sift

Uncertain

0.021

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.10

MPC

0.29

ClinPred

0.024

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.32

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over