Variant 1-207321863-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The ENST00000367064.9(CD55):c.98G>A(p.Trp33Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,370,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

CD55
ENST00000367064.9 stop_gained, splice_region

Scores

Splicing: ADA: 0.00002263

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -1.27

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 links:

LOC107985251 (HGNC:):

LOC107985251 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-207321863-G-A is Pathogenic according to our data. Variant chr1-207321863-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3338382.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5 linkuse as main transcript	c.98G>A	p.Trp33Ter	stop_gained, splice_region_variant	1/10	ENST00000367064.9	NP_000565.1
LOC107985251	XR_007066838.1 linkuse as main transcript	n.267C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9 linkuse as main transcript	c.98G>A	p.Trp33Ter	stop_gained, splice_region_variant	1/10	1	NM_000574.5	ENSP00000356031	P2	P08174-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000584

AC:

AN:

1370064

Hom.:

Cov.:

AF XY:

0.00000296

AC XY:

AN XY:

675462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000747

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Protein-losing enteropathy

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Jul 11, 2024

ACMG Criteria: PVS1,PM2_SUP,PM3_SUP,PP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Benign

0.92

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.069

MutationTaster

Benign

1.0

A;A;A;A;A;A;A;A

Vest4

0.63

ClinPred

0.95

GERP RS

-5.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.058

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over