rs12917189

chr15-42731284-T-Achr15-42731284-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138477.4(CDAN1):c.1787A>T(p.Gln596Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. Q596R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDAN1 NM_138477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033655435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDAN1	NM_138477.4	c.1787A>T	p.Gln596Leu	missense_variant	12/28	ENST00000356231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDAN1	ENST00000356231.4	c.1787A>T	p.Gln596Leu	missense_variant	12/28	1	NM_138477.4	P1
CDAN1	ENST00000643434.1	c.*965A>T		3_prime_UTR_variant, NMD_transcript_variant	10/25

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461838 Hom.: 0 Cov.: 38 AF XY: 0.00000688 AC XY: 5 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-1.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.18
Sift	Benign	0.70	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.27		Loss of disorder (P = 0.0491);
MVP		0.15
MPC		0.084
ClinPred		0.37	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.064
gMVP		0.44

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

Other links and lift over

dbSNP: rs12917189; hg19: chr15-43023482;