chr15-42724234-T-TAAAC

Variant names:

• chr15-42724234-T-TAAAC
• rs767935615
• NM_138477.4:c.*253_*256dupGTTT

Variant summary

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

The NM_138477.4(CDAN1):​c.*253_*256dupGTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 337,922 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CDAN1 NM_138477.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 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

ENSG00000278769 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*253_*256dupGTTT		3_prime_UTR	Exon 28 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.*253_*256dupGTTT		3_prime_UTR	Exon 28 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*839_*842dupGTTT		non_coding_transcript_exon	Exon 15 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000562465.5	TSL:1	n.*839_*842dupGTTT		3_prime_UTR	Exon 15 of 15	ENSP00000454246.1	H3BM60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000118 AC: 4 AN: 337922 Hom.: 0 Cov.: 3 AF XY: 0.0000167 AC XY: 3 AN XY: 179826

African (AFR) AF: 0.00 AC: 0 AN: 9846

American (AMR) AF: 0.00 AC: 0 AN: 15462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9948

East Asian (EAS) AF: 0.00 AC: 0 AN: 20038

South Asian (SAS) AF: 0.0000444 AC: 2 AN: 45014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1392

European-Non Finnish (NFE) AF: 0.0000101 AC: 2 AN: 198288

Other (OTH) AF: 0.00 AC: 0 AN: 18908

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767935615; hg19: chr15-43016432;