rs1555415486

Variant names:

• chr15-42731279-GC-TCTTCAAGCCCAGGGCAAGA
• rs1555415486
• NM_138477.4:c.1791_1792delGCinsTCTTGCCCTGGGCTTGAAGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_138477.4(CDAN1):​c.1791_1792delGCinsTCTTGCCCTGGGCTTGAAGA​(p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle) variant causes a missense, disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDAN1 NM_138477.4 missense, disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital dyserythropoietic anemia type 1

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

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

ACMG classification

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

• PM4: Nonframeshift variant in NON repetitive region in NM_138477.4.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.1791_1792delGCinsTCTTGCCCTGGGCTTGAAGA	p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle	missense disruptive_inframe_insertion	N/A	NP_612486.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.1791_1792delGCinsTCTTGCCCTGGGCTTGAAGA	p.Glu597_Leu598delinsAspLeuAlaLeuGlyLeuLysIle	missense disruptive_inframe_insertion	N/A	ENSP00000348564.3
	CDAN1	ENST00000643434.1		n.*969_*970delGCinsTCTTGCCCTGGGCTTGAAGA		non_coding_transcript_exon	Exon 10 of 25	ENSP00000494699.1
	CDAN1	ENST00000643434.1		n.*969_*970delGCinsTCTTGCCCTGGGCTTGAAGA		3_prime_UTR	Exon 10 of 25	ENSP00000494699.1

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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

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

Other links and lift over

dbSNP: rs1555415486; hg19: chr15-43023477;