rs12905385

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2408-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.204 in 1,613,582 control chromosomes in the GnomAD database, including 37,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5076 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31974 hom. )

Consequence

CDAN1
NM_138477.4 splice_region, intron

Scores

Splicing: ADA: 0.003605

Clinical Significance

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

Conservation

PhyloP100: 6.03

Publications

15 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 (BayesDel_noAF=-0.47).

BP6

Variant 15-42729365-G-A is Benign according to our data. Variant chr15-42729365-G-A is described in ClinVar as Benign. ClinVar VariationId is 262371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.2408-3C>T		splice_region_variant, intron_variant	Intron 17 of 27	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDAN1	ENST00000356231.4 link	c.2408-3C>T	splice_region_variant, intron_variant	Intron 17 of 27	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000562465.5 link	n.401-3C>T	splice_region_variant, intron_variant	Intron 4 of 14	1		ENSP00000454246.1	H3BM60
CDAN1	ENST00000643434.1 link	n.*1586-3C>T	splice_region_variant, intron_variant	Intron 15 of 24			ENSP00000494699.1	A0A2R8Y5C2

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36270

AN:

152010

Hom.:

5075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0545

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.221

GnomAD2 exomes

AF:

0.201

AC:

50428

AN:

250652

AF XY:

0.209

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.0934

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0562

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.200

AC:

292280

AN:

1461454

Hom.:

31974

Cov.:

AF XY:

0.204

AC XY:

148518

AN XY:

727038

show subpopulations

African (AFR)

AF:

0.379

AC:

12672

AN:

33466

American (AMR)

AF:

0.0992

AC:

4435

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6579

AN:

26132

East Asian (EAS)

AF:

0.0699

AC:

2774

AN:

39700

South Asian (SAS)

AF:

0.338

AC:

29155

AN:

86244

European-Finnish (FIN)

AF:

0.232

AC:

12390

AN:

53412

Middle Eastern (MID)

AF:

0.227

AC:

1306

AN:

5762

European-Non Finnish (NFE)

AF:

0.189

AC:

210287

AN:

1111648

Other (OTH)

AF:

0.210

AC:

12682

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13548

27096

40644

54192

67740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7536

15072

22608

30144

37680

<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:

0.239

AC:

36292

AN:

152128

Hom.:

5076

Cov.:

AF XY:

0.239

AC XY:

17759

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.376

AC:

15584

AN:

41456

American (AMR)

AF:

0.136

AC:

2078

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3470

East Asian (EAS)

AF:

0.0548

AC:

284

AN:

5184

South Asian (SAS)

AF:

0.323

AC:

1556

AN:

4824

European-Finnish (FIN)

AF:

0.230

AC:

2441

AN:

10596

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.189

AC:

12881

AN:

67992

Other (OTH)

AF:

0.219

AC:

462

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1332

2664

3995

5327

6659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.202

Hom.:

5446

Bravo

AF:

0.234

Asia WGS

AF:

0.194

AC:

674

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Anemia, congenital dyserythropoietic, type 1a

Benign:1

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

6.0

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0036

dbscSNV1_RF

Benign

0.12

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