rs1135402916

Variant names:

• chr1-207322430-AA-CCTT
• rs1135402916
• NM_000574.5:c.149_150delAAinsCCTT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000574.5(CD55):​c.149_150delAAinsCCTT​(p.Glu50AlafsTer12) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E50K) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD55 NM_000574.5 frameshift, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.197
• Publications: 0 publications found

Genes affected

CD55 (HGNC:2665): (CD55 molecule (Cromer blood group)) This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins. [provided by RefSeq, Jul 2014]

CD55 Gene-Disease associations (from GenCC):

• protein-losing enteropathy

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-207322430-AA-CCTT is Pathogenic according to our data. Variant chr1-207322430-AA-CCTT is described in ClinVar as Pathogenic. ClinVar VariationId is 431761.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000574.5. 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
	CD55	NM_000574.5	MANE Select	c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 10	NP_000565.1	P08174-1
	CD55	NM_001300902.2		c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 10	NP_001287831.1	B1AP13
	CD55	NM_001114752.3		c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 11	NP_001108224.1	P08174-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 10	ENSP00000356031.4	P08174-1
	CD55	ENST00000367063.6	TSL:1	c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 10	ENSP00000356030.2	B1AP13
	CD55	ENST00000314754.12	TSL:1	c.149_150delAAinsCCTT	p.Glu50AlafsTer12	frameshift missense	Exon 2 of 11	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Complement hyperactivation-angiopathic thrombosis-protein-losing enteropathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1135402916; hg19: chr1-207495775;