15-42726361-C-A

Variant names:

• chr15-42726361-C-A
• rs28661826
• NM_138477.4:c.3153G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138477.4(CDAN1):​c.3153G>T​(p.Glu1051Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,445,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E1051G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDAN1 NM_138477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 5 publications found

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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• congenital dyserythropoietic anemia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital dyserythropoietic anemia

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

ENSG00000274403 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08968523).

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.3153G>T	p.Glu1051Asp	missense	Exon 24 of 28	NP_612486.2	Q8IWY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.3153G>T	p.Glu1051Asp	missense	Exon 24 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*55G>T		non_coding_transcript_exon	Exon 11 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000562465.5	TSL:1	n.*55G>T		3_prime_UTR	Exon 11 of 15	ENSP00000454246.1	H3BM60

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000453 AC: 1 AN: 220590 AF XY: 0.00000838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1445870 Hom.: 0 Cov.: 33 AF XY: 0.00000418 AC XY: 3 AN XY: 717846

African (AFR) AF: 0.00 AC: 0 AN: 33164

American (AMR) AF: 0.00 AC: 0 AN: 42344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25722

East Asian (EAS) AF: 0.00 AC: 0 AN: 38870

South Asian (SAS) AF: 0.00 AC: 0 AN: 83572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104604

Other (OTH) AF: 0.00 AC: 0 AN: 59744

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.47
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.26	T
Sift4G	Benign	0.61	T
Polyphen		0.0040	B
Vest4		0.28
MutPred		0.16		Loss of disorder (P = 0.1997)
MVP		0.40
MPC		0.075
ClinPred		0.094	T
GERP RS		0.60
Varity_R		0.081
gMVP		0.48
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs28661826; hg19: chr15-43018559;