15-42736485-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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=0.004267454).

BP6

Variant 15-42736485-C-T is Benign according to our data. Variant chr15-42736485-C-T is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.386G>A	p.Arg129His	missense_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.386G>A	p.Arg129His	missense_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000643434.1 link	n.91-404G>A		intron_variant	Intron 1 of 24			ENSP00000494699.1	A0A2R8Y5C2
CDAN1	ENST00000563260.1 link	c.*77G>A		downstream_gene_variant		3		ENSP00000455536.1	H3BPZ6

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

GnomAD3 exomes

AF:

0.0129

AC:

761

AN:

59214

Hom.:

AF XY:

0.00937

AC XY:

315

AN XY:

33634

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 SAS exome

AF:

0.000109

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

Gnomad4 AFR exome

AF:

0.000347

Gnomad4 AMR exome

AF:

0.0504

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0191

Gnomad4 SAS exome

AF:

0.0000772

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152048

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00645

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000326

Hom.:

Bravo

AF:

0.00453

ExAC

AF:

0.00310

AC:

186

Asia WGS

AF:

0.00377

AC:

AN:

3466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital dyserythropoietic anemia, type I

Benign:1

Apr 28, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Anemia, congenital dyserythropoietic, type 1a

Benign:1

Nov 15, 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

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

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

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

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

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