15-42731279-GC-TCTTCAAGCCCAGGGCAAGA

Position:

• chr15-42731279-GC-TCTTCAAGCCCAGGGCAAGA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000356231.4(CDAN1):​c.1791_1792delinsTCTTGCCCTGGGCTTGAAGA​(p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle) variant causes a protein altering change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDAN1 ENST00000356231.4 protein_altering
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000356231.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.1791_1792delinsTCTTGCCCTGGGCTTGAAGA	p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle	protein_altering_variant	12/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.1791_1792delinsTCTTGCCCTGGGCTTGAAGA	p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle	protein_altering_variant	12/28	1	NM_138477.4	ENSP00000348564	P1
CDAN1	ENST00000643434.1	c.*969_*970delinsTCTTGCCCTGGGCTTGAAGA		3_prime_UTR_variant, NMD_transcript_variant	10/25			ENSP00000494699

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 12, 2017

The p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle (NM138477.2 c.1791_1792delinsT CTTGCCCTGGGCTTGAAGA) variant in CDAN1 has not been reported in individuals with Congenital dyserythropoietic anaemia. It has been identified in 2/111708 Europea n chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs759000974 and rs767149931); note, this variant is represente d as two independent events in gnomAD. This variant is a deletion of 2 amino aci ds and an insertion of 8 amino acids at position 597 and is not predicted to alt er the protein reading-frame. However, it is unclear if this insertion/deletion will impact the protein. In summary, the clinical significance of the p.Glu597_L eu598delinsAspLeuAlaLeuGlyLeuLysIle variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555415486; hg19: chr15-43023477;