rs193921034

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001281956.2(CSMD2):​c.7808G>T​(p.Arg2603Leu) variant causes a missense change. 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 Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CSMD2
NM_001281956.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.16

Publications

4 publications found
Variant links:
Genes affected
CSMD2 (HGNC:19290): (CUB and Sushi multiple domains 2) The protein encoded by this gene is thought to be involved in the control of complement cascade of the immune system. Defects in this gene have been associated with schizophrenia. This gene may act as a tumor suppressor for colorectal cancer. [provided by RefSeq, Jan 2020]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSMD2NM_001281956.2 linkc.7808G>T p.Arg2603Leu missense_variant Exon 51 of 71 ENST00000373381.9 NP_001268885.1 Q7Z408-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSMD2ENST00000373381.9 linkc.7808G>T p.Arg2603Leu missense_variant Exon 51 of 71 1 NM_001281956.2 ENSP00000362479.4 Q7Z408-4
CSMD2ENST00000373388.7 linkc.7814G>T p.Arg2605Leu missense_variant Exon 52 of 70 1 ENSP00000362486.3 Q7Z408-1
CSMD2ENST00000619121.4 linkc.7688G>T p.Arg2563Leu missense_variant Exon 51 of 71 5 ENSP00000483463.1 A0A087X0K4
CSMD2ENST00000465819.1 linkc.131G>T p.Arg44Leu missense_variant Exon 2 of 5 5 ENSP00000509557.1 A0A8I5KWH5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1419668
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
702006
African (AFR)
AF:
0.00
AC:
0
AN:
32878
American (AMR)
AF:
0.00
AC:
0
AN:
43166
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25452
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38724
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78920
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5518
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1084124
Other (OTH)
AF:
0.00
AC:
0
AN:
58276
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Prostate cancer Uncertain:1
-
Science for Life laboratory, Karolinska Institutet
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T;T
Eigen
Benign
0.058
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.75
D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.2
.;M;.
PhyloP100
6.2
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.3
D;.;.
REVEL
Uncertain
0.38
Sift
Benign
0.20
T;.;.
Sift4G
Benign
0.21
T;T;T
Polyphen
0.013
.;B;.
Vest4
0.88
MutPred
0.68
.;Loss of disorder (P = 0.1146);.;
MVP
0.47
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.40
gMVP
0.63
Mutation Taster
=34/66
disease causing

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

Other links and lift over

dbSNP: rs193921034; hg19: chr1-34037281; COSMIC: COSV53912174; API