rs1184664313

Variant names:

• chr1-33523360-C-G
• NM_001281956.2:c.10456G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-33523360-C-G
• chr1-33523360-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001281956.2(CSMD2):​c.10456G>C​(p.Val3486Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V3486M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSMD2 NM_001281956.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10894865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.10456G>C	p.Val3486Leu	missense_variant	Exon 67 of 71	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.10456G>C	p.Val3486Leu	missense_variant	Exon 67 of 71	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.10024G>C	p.Val3342Leu	missense_variant	Exon 66 of 70	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.10336G>C	p.Val3446Leu	missense_variant	Exon 67 of 71	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451836 Hom.: 0 Cov.: 26 AF XY: 0.00000138 AC XY: 1 AN XY: 722886

Gnomad4 AFR exome AF: 0.0000301

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.022	.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.054
Sift	Benign	0.12	T;.;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.17
MutPred		0.47		.;Gain of loop (P = 0.0851);.;
MVP		0.25
ClinPred		0.090	T
GERP RS		2.3
Varity_R		0.051
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-33988960;