Genetic Variant CDAN1:p.Gln107Arg (chr15-42736551-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138477.4(CDAN1):c.320A>G(p.Gln107Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,332,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q107L) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.547

Publications

27 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0516105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.320A>G	p.Gln107Arg	missense_variant	Exon 2 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CDAN1	ENST00000356231.4 link	c.320A>G	p.Gln107Arg	missense_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1 link	n.90+462A>G		intron_variant	Intron 1 of 24			ENSP00000494699.1
CDAN1	ENST00000563260.1 link	c.*11A>G		downstream_gene_variant		3		ENSP00000455536.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.50e-7

AC:

AN:

1332720

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

657340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26718

American (AMR)

AF:

0.00

AC:

AN:

28532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23250

East Asian (EAS)

AF:

0.00

AC:

AN:

29514

South Asian (SAS)

AF:

0.00

AC:

AN:

73674

European-Finnish (FIN)

AF:

0.0000264

AC:

AN:

37950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4386

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1053658

Other (OTH)

AF:

0.00

AC:

AN:

55038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.43

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.067

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.15

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

PhyloP100

-0.55

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.090

REVEL

Benign

0.17

Sift

Benign

0.59

Sift4G

Benign

0.53

Polyphen

0.016

Vest4

0.014

MutPred

0.11

Gain of methylation at Q107 (P = 0.0145);

MVP

0.17

MPC

0.91

ClinPred

0.036

GERP RS

-1.2

Varity_R

0.026

gMVP

0.42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over