1-207331243-G-C

Position:

• chr1-207331243-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The ENST00000367064.9(CD55):​c.800G>C​(p.Cys267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD55 ENST00000367064.9 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.25

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988
• PP5: Variant 1-207331243-G-C is Pathogenic according to our data. Variant chr1-207331243-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 431762.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-207331243-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5	c.800G>C	p.Cys267Ser	missense_variant	6/10	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.800G>C	p.Cys267Ser	missense_variant	6/10	1	NM_000574.5	ENSP00000356031	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Protein-losing enteropathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.68	D;.;T;.;.;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.85	T;T;D;T;T;D;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	5.1	H;.;.;H;H;.;H
MutationTaster	Benign	0.99	D;N;N;N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-8.3	D;D;D;.;D;.;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0030	D;D;D;.;D;.;.
Sift4G	Uncertain	0.011	D;D;D;.;D;D;.
Polyphen		1.0	D;D;D;.;D;.;.
Vest4		0.95
MutPred		0.93		Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);.;Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);
MVP		0.95
MPC		0.62
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.99
gMVP		0.98

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: rs1135402917; hg19: chr1-207504588;