rs2281597

Positions:

• chr1-33894257-G-C
• chr1-33894257-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373381.9(CSMD2):​c.920+23837C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,042 control chromosomes in the GnomAD database, including 51,445 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 0.82 (51445 hom., cov: 30)
• Consequence: CSMD2 ENST00000373381.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.920+23837C>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.920+23837C>G		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.800+23837C>G		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.800+23837C>G		intron_variant		5		ENSP00000483463	A2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124020 AN: 151924 Hom.: 51381 Cov.: 30

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.817 AC: 124143 AN: 152042 Hom.: 51445 Cov.: 30 AF XY: 0.818 AC XY: 60813 AN XY: 74310

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.794

Alfa AF: 0.761 Hom.: 24631

Bravo AF: 0.829

Asia WGS AF: 0.909 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.46

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: rs2281597; hg19: chr1-34359858;