rs193921034

Variant names:

• chr1-33571681-C-A
• rs193921034
• NM_001281956.2:c.7808G>T
• CSMD2 p.Arg2603Leu

Your query was ambiguous. Multiple possible variants found:

• chr1-33571681-C-A
• chr1-33571681-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.16
• Publications: 4 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281956.2. 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
	CSMD2	NM_001281956.2	MANE Select	c.7808G>T	p.Arg2603Leu	missense	Exon 51 of 71	NP_001268885.1	Q7Z408-4
	CSMD2	NM_052896.5		c.7814G>T	p.Arg2605Leu	missense	Exon 52 of 70	NP_443128.2	Q7Z408-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD2	ENST00000373381.9	TSL:1 MANE Select	c.7808G>T	p.Arg2603Leu	missense	Exon 51 of 71	ENSP00000362479.4	Q7Z408-4
	CSMD2	ENST00000373388.7	TSL:1	c.7814G>T	p.Arg2605Leu	missense	Exon 52 of 70	ENSP00000362486.3	Q7Z408-1
	CSMD2	ENST00000619121.4	TSL:5	c.7688G>T	p.Arg2563Leu	missense	Exon 51 of 71	ENSP00000483463.1	A0A087X0K4

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

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.058
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.75	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
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193921034;

hg19: chr1-34037281;

COSMIC: COSV53912174;