chr15-42730963-C-T

Position:

chr15-42730963-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138477.4(CDAN1):c.1969G>A(p.Gly657Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,614,064 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 554 hom., cov: 32)

Exomes 𝑓: 0.011 ( 633 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.49

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=0.0014235973).

BP6

Variant 15-42730963-C-T is Benign according to our data. Variant chr15-42730963-C-T is described in ClinVar as [Benign]. Clinvar id is 262368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4 linkuse as main transcript	c.1969G>A	p.Gly657Ser	missense_variant	13/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4 linkuse as main transcript	c.1969G>A	p.Gly657Ser	missense_variant	13/28	1	NM_138477.4	ENSP00000348564	P1	Q8IWY9-2
CDAN1	ENST00000643434.1 linkuse as main transcript	c.*1147G>A		3_prime_UTR_variant, NMD_transcript_variant	11/25			ENSP00000494699

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

7864

AN:

152116

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0573

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.0396

GnomAD3 exomes

AF:

0.0214

AC:

5373

AN:

251260

Hom.:

284

AF XY:

0.0188

AC XY:

2555

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.00954

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.0638

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0107

AC:

15665

AN:

1461830

Hom.:

633

Cov.:

AF XY:

0.0106

AC XY:

7717

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0505

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00419

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0517

AC:

7878

AN:

152234

Hom.:

554

Cov.:

AF XY:

0.0505

AC XY:

3761

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0575

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00447

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0603

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.160

AC:

707

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.0244

AC:

2959

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 13, 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

Oct 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.094

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.14

MutationTaster

Benign

0.94

PrimateAI

Benign

0.40

PROVEAN

Benign

0.83

REVEL

Benign

0.21

Sift

Benign

0.77

Sift4G

Benign

0.55

Polyphen

0.077

Vest4

0.10

MPC

0.092

ClinPred

0.016

GERP RS

4.7

Varity_R

0.042

gMVP

0.30

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

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