15-42736551-T-C

Position:

• chr15-42736551-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.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. 14/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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=0.0516105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.320A>G	p.Gln107Arg	missense_variant	2/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.320A>G	p.Gln107Arg	missense_variant	2/28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1	n.90+462A>G		intron_variant				ENSP00000494699.1
CDAN1	ENST00000563260.1	c.*11A>G		downstream_gene_variant		3		ENSP00000455536.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1332720 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 657340

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: 0.0000264

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.43
DANN	Benign	0.40
DEOGEN2	Benign	0.067	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.15	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.17
Sift	Benign	0.59	T
Sift4G	Benign	0.53	T
Polyphen		0.016	B
Vest4		0.014
MutPred		0.11		Gain of methylation at Q107 (P = 0.0145);
MVP		0.17
MPC		0.91
ClinPred		0.036	T
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

LitVar

Other links and lift over

dbSNP: rs4265781; hg19: chr15-43028749;