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:

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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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.320A>G	p.Gln107Arg	missense	Exon 2 of 28	NP_612486.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.320A>G	p.Gln107Arg	missense	Exon 2 of 28	ENSP00000348564.3
CDAN1	ENST00000913682.1		c.320A>G	p.Gln107Arg	missense	Exon 2 of 28	ENSP00000583741.1
CDAN1	ENST00000913683.1		c.320A>G	p.Gln107Arg	missense	Exon 2 of 28	ENSP00000583742.1

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over