rs504527

Positions:

• chr1-34008007-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.517+24587T>G		intron_variant		ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.517+24587T>G		intron_variant		1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.397+24587T>G		intron_variant		1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.397+24587T>G		intron_variant		5		ENSP00000483463.1

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

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.605

Alfa AF: 0.564 Hom.: 11724

Bravo AF: 0.622

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.76

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

LitVar

Other links and lift over

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