Genetic Variant NM_000574.5:c.800G>C (chr1-207331243-G-C) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_000574.5(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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CD55
NM_000574.5 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 3.25

Publications

3 publications found

Variant links:

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)

CD55 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 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 VariationId is 431762.Status of the report is criteria_provided_single_submitter, 1 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD55	NM_000574.5	MANE Select	c.800G>C	p.Cys267Ser	missense	Exon 6 of 10	NP_000565.1	P08174-1
CD55	NM_001300902.2		c.800G>C	p.Cys267Ser	missense	Exon 6 of 10	NP_001287831.1	B1AP13
CD55	NM_001114752.3		c.800G>C	p.Cys267Ser	missense	Exon 6 of 11	NP_001108224.1	P08174-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD55	ENST00000367064.9	TSL:1 MANE Select	c.800G>C	p.Cys267Ser	missense	Exon 6 of 10	ENSP00000356031.4	P08174-1
CD55	ENST00000367063.6	TSL:1	c.800G>C	p.Cys267Ser	missense	Exon 6 of 10	ENSP00000356030.2	B1AP13
CD55	ENST00000314754.12	TSL:1	c.800G>C	p.Cys267Ser	missense	Exon 6 of 11	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

COMPLEMENT HYPERACTIVATION, ANGIOPATHIC THROMBOSIS, AND PROTEIN-LOSING ENTEROPATHY (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.041

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.39

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

5.1

PhyloP100

3.3

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-8.3

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.95

MutPred

0.93

Gain of disorder (P = 0.0107)

MVP

0.95

MPC

0.62

ClinPred

1.0

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.99

gMVP

0.98

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over