NM_138477.4:c.386G>A

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.386G>A(p.Arg129His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,447,760 control chromosomes in the GnomAD database, including 49 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 46 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.741

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004267454).

BP6

Variant 15-42736485-C-T is Benign according to our data. Variant chr15-42736485-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 21752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00215 (327/152048) while in subpopulation AMR AF = 0.0171 (262/15292). AF 95% confidence interval is 0.0154. There are 3 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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.386G>A	p.Arg129His	missense	Exon 2 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.386G>A	p.Arg129His	missense	Exon 2 of 28	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000913682.1		c.386G>A	p.Arg129His	missense	Exon 2 of 28	ENSP00000583741.1
CDAN1	ENST00000913683.1		c.386G>A	p.Arg129His	missense	Exon 2 of 28	ENSP00000583742.1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

325

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00643

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0129

AC:

761

AN:

59214

AF XY:

0.00937

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0758

Gnomad ASJ exome

AF:

0.000356

Gnomad EAS exome

AF:

0.00953

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00872

GnomAD4 exome

AF:

0.00131

AC:

1699

AN:

1295712

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

739

AN XY:

636472

show subpopulations

African (AFR)

AF:

0.000347

AC:

AN:

25926

American (AMR)

AF:

0.0504

AC:

1000

AN:

19834

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

19634

East Asian (EAS)

AF:

0.0191

AC:

591

AN:

30958

South Asian (SAS)

AF:

0.0000772

AC:

AN:

64736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4412

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1039698

Other (OTH)

AF:

0.00111

AC:

AN:

53316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

182

273

364

455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152048

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41550

American (AMR)

AF:

0.0171

AC:

262

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00645

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67932

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000326

Hom.:

Bravo

AF:

0.00453

ExAC

AF:

0.00310

AC:

186

Asia WGS

AF:

0.00377

AC:

AN:

3466

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Anemia, congenital dyserythropoietic, type 1a (1)

Congenital dyserythropoietic anemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.047

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.45

MutationAssessor

Benign

2.0

PhyloP100

0.74

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.54

REVEL

Benign

0.26

Sift

Uncertain

0.017

Sift4G

Benign

0.070

Polyphen

0.23

Vest4

0.20

MPC

2.2

ClinPred

0.066

GERP RS

4.2

Varity_R

0.13

gMVP

0.53

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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