NM_138477.4:c.1787A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_138477.4(CDAN1):c.1787A>G(p.Gln596Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,810 control chromosomes in the GnomAD database, including 70,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 17757 hom., cov: 32)

Exomes 𝑓: 0.24 ( 52332 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.17

Publications

41 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
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 -18 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_138477.4

BP4

Computational evidence support a benign effect (MetaRNN=5.55778E-7).

BP6

Variant 15-42731284-T-C is Benign according to our data. Variant chr15-42731284-T-C is described in ClinVar as Benign. ClinVar VariationId is 21747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.1787A>G	p.Gln596Arg	missense	Exon 12 of 28	NP_612486.2	Q8IWY9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.1787A>G	p.Gln596Arg	missense	Exon 12 of 28	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000913682.1		c.1790A>G	p.Gln597Arg	missense	Exon 12 of 28	ENSP00000583741.1
CDAN1	ENST00000913683.1		c.1787A>G	p.Gln596Arg	missense	Exon 12 of 28	ENSP00000583742.1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59800

AN:

151922

Hom.:

17698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.343

GnomAD2 exomes

AF:

0.277

AC:

69759

AN:

251406

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.846

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.241

AC:

351814

AN:

1461770

Hom.:

52332

Cov.:

AF XY:

0.246

AC XY:

178665

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.863

AC:

28883

AN:

33480

American (AMR)

AF:

0.136

AC:

6091

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7876

AN:

26136

East Asian (EAS)

AF:

0.246

AC:

9785

AN:

39700

South Asian (SAS)

AF:

0.438

AC:

37798

AN:

86256

European-Finnish (FIN)

AF:

0.255

AC:

13590

AN:

53394

Middle Eastern (MID)

AF:

0.303

AC:

1746

AN:

5768

European-Non Finnish (NFE)

AF:

0.206

AC:

229351

AN:

1111918

Other (OTH)

AF:

0.276

AC:

16694

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

15963

31926

47889

63852

79815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8346

16692

25038

33384

41730

<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:

0.394

AC:

59910

AN:

152040

Hom.:

17757

Cov.:

AF XY:

0.391

AC XY:

29064

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.835

AC:

34652

AN:

41476

American (AMR)

AF:

0.197

AC:

3016

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1054

AN:

3470

East Asian (EAS)

AF:

0.254

AC:

1312

AN:

5168

South Asian (SAS)

AF:

0.426

AC:

2045

AN:

4802

European-Finnish (FIN)

AF:

0.255

AC:

2692

AN:

10560

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14255

AN:

67970

Other (OTH)

AF:

0.339

AC:

716

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1289

2579

3868

5158

6447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.268

Hom.:

24779

Bravo

AF:

0.403

TwinsUK

AF:

0.201

AC:

745

ALSPAC

AF:

0.202

AC:

780

ESP6500AA

AF:

0.819

AC:

3608

ESP6500EA

AF:

0.210

AC:

1805

ExAC

AF:

0.293

AC:

35595

Asia WGS

AF:

0.356

AC:

1237

AN:

3478

EpiCase

AF:

0.209

EpiControl

AF:

0.210

ClinVar

ClinVar submissions

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

0.059

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.077

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.074

MetaRNN

Benign

5.6e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.95

PhyloP100

2.2

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.12

REVEL

Benign

0.25

Sift

Benign

0.51

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.031

MPC

0.087

ClinPred

0.0050

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.30

Mutation Taster

=99/1

polymorphism (auto)

(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

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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

Computational scores

Splicing

Publications

Other links and lift over