chr15-42736313-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138477.4(CDAN1):c.558C>G(p.Pro186Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,612,410 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 618 hom., cov: 32)

Exomes 𝑓: 0.012 ( 805 hom. )

Consequence

CDAN1
NM_138477.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0420

Publications

6 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 15-42736313-G-C is Benign according to our data. Variant chr15-42736313-G-C is described in ClinVar as [Benign]. Clinvar id is 262379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.042 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.558C>G	p.Pro186Pro	synonymous_variant	Exon 2 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.558C>G	p.Pro186Pro	synonymous_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000643434.1 link	n.91-232C>G		intron_variant	Intron 1 of 24			ENSP00000494699.1	A0A2R8Y5C2
CDAN1	ENST00000563260.1 link	c.*249C>G		downstream_gene_variant		3		ENSP00000455536.1	H3BPZ6

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8593

AN:

152026

Hom.:

616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00507

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0246

AC:

6059

AN:

246502

AF XY:

0.0225

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.00952

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.0649

Gnomad FIN exome

AF:

0.000378

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0125

AC:

18224

AN:

1460268

Hom.:

805

Cov.:

AF XY:

0.0126

AC XY:

9119

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.188

AC:

6301

AN:

33458

American (AMR)

AF:

0.0113

AC:

504

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0324

AC:

845

AN:

26120

East Asian (EAS)

AF:

0.0512

AC:

2033

AN:

39682

South Asian (SAS)

AF:

0.0288

AC:

2485

AN:

86196

European-Finnish (FIN)

AF:

0.000340

AC:

AN:

52878

Middle Eastern (MID)

AF:

0.0160

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00420

AC:

4670

AN:

1111132

Other (OTH)

AF:

0.0212

AC:

1276

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

940

1881

2821

3762

4702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.0566

AC:

8613

AN:

152142

Hom.:

618

Cov.:

AF XY:

0.0547

AC XY:

4068

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.176

AC:

7309

AN:

41504

American (AMR)

AF:

0.0217

AC:

332

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.0582

AC:

299

AN:

5140

South Asian (SAS)

AF:

0.0268

AC:

129

AN:

4822

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00506

AC:

344

AN:

67976

Other (OTH)

AF:

0.0411

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

366

732

1099

1465

1831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0106

Hom.:

Bravo

AF:

0.0632

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 13, 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 08, 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

-0.60

CADD

Benign

5.5

(source)

DANN

Benign

0.68

PhyloP100

-0.042

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over