rs8023524

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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:5

Conservation

PhyloP100: 0.967

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 21749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42728785-G-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDAN1	NM_138477.4 linkuse as main transcript	c.2671C>T	p.Arg891Cys	missense_variant	20/28	ENST00000356231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDAN1	ENST00000356231.4 linkuse as main transcript	c.2671C>T	p.Arg891Cys	missense_variant	20/28	1	NM_138477.4	P1	Q8IWY9-2
CDAN1	ENST00000562465.5 linkuse as main transcript	c.664C>T	p.Arg222Cys	missense_variant, NMD_transcript_variant	7/15	1
CDAN1	ENST00000643434.1 linkuse as main transcript	c.*1849C>T		3_prime_UTR_variant, NMD_transcript_variant	18/25

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

GnomAD3 exomes

AF:

0.208

AC:

52115

AN:

251126

Hom.:

6661

AF XY:

0.214

AC XY:

29088

AN XY:

135760

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 SAS exome

AF:

0.351

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

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.0809

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.255

AC:

38778

AN:

152108

Hom.:

6050

Cov.:

AF XY:

0.255

AC XY:

18945

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.0629

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.196

Hom.:

6638

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

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 29031773) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital dyserythropoietic anemia, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

Cadd

Benign

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

MutationTaster

Benign

0.16

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over