rs149656829

Variant names:

• chr1-33527223-G-A
• rs149656829
• NM_001281956.2:c.10207C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-33527223-G-A
• chr1-33527223-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001281956.2(CSMD2):​c.10207C>T​(p.Arg3403Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000959 in 1,613,962 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (2 hom.)
• Consequence: CSMD2 NM_001281956.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 8 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07296166).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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.10207C>T	p.Arg3403Trp	missense	Exon 65 of 71	NP_001268885.1	Q7Z408-4
	CSMD2	NM_052896.5		c.9775C>T	p.Arg3259Trp	missense	Exon 64 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.10207C>T	p.Arg3403Trp	missense	Exon 65 of 71	ENSP00000362479.4	Q7Z408-4
	CSMD2	ENST00000373388.7	TSL:1	c.9775C>T	p.Arg3259Trp	missense	Exon 64 of 70	ENSP00000362486.3	Q7Z408-1
	CSMD2	ENST00000619121.4	TSL:5	c.10087C>T	p.Arg3363Trp	missense	Exon 65 of 71	ENSP00000483463.1	A0A087X0K4

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000684 AC: 172 AN: 251362 AF XY: 0.000707

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000986 AC: 1441 AN: 1461808 Hom.: 2 Cov.: 30 AF XY: 0.000968 AC XY: 704 AN XY: 727210

African (AFR) AF: 0.0000896 AC: 3 AN: 33474

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86246

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00121 AC: 1340 AN: 1111944

Other (OTH) AF: 0.000695 AC: 42 AN: 60396

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000740 AC XY: 55 AN XY: 74332

African (AFR) AF: 0.000314 AC: 13 AN: 41434

American (AMR) AF: 0.000262 AC: 4 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00109 Hom.: 2

Bravo AF: 0.000688

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000799 AC: 97

EpiCase AF: 0.00120

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.022	D
Sift4G	Benign	0.15	T
Polyphen		0.74	P
Vest4		0.58
MVP		0.48
ClinPred		0.12	T
GERP RS		5.4
Varity_R		0.21
gMVP		0.58
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs149656829; hg19: chr1-33992823; COSMIC: COSV53913002;