rs504527

Variant names:

• chr1-34008007-A-C
• rs504527
• NM_001281956.2:c.517+24587T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281956.2(CSMD2):​c.517+24587T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,042 control chromosomes in the GnomAD database, including 30,200 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30200 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

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.517+24587T>G		intron	N/A	NP_001268885.1	Q7Z408-4
	CSMD2	NM_052896.5		c.397+24587T>G		intron	N/A	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.517+24587T>G		intron	N/A	ENSP00000362479.4	Q7Z408-4
	CSMD2	ENST00000373388.7	TSL:1	c.397+24587T>G		intron	N/A	ENSP00000362486.3	Q7Z408-1
	CSMD2	ENST00000619121.4	TSL:5	c.397+24587T>G		intron	N/A	ENSP00000483463.1	A0A087X0K4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93634 AN: 151924 Hom.: 30165 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.616 AC: 93729 AN: 152042 Hom.: 30200 Cov.: 32 AF XY: 0.620 AC XY: 46037 AN XY: 74304

African (AFR) AF: 0.797 AC: 33051 AN: 41478

American (AMR) AF: 0.560 AC: 8560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1898 AN: 3466

East Asian (EAS) AF: 0.803 AC: 4147 AN: 5164

South Asian (SAS) AF: 0.730 AC: 3511 AN: 4812

European-Finnish (FIN) AF: 0.540 AC: 5703 AN: 10560

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34856 AN: 67968

Other (OTH) AF: 0.605 AC: 1271 AN: 2100

Alfa AF: 0.563 Hom.: 13131

Bravo AF: 0.622

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs504527; hg19: chr1-34473608; COSMIC: COSV53894119;