1-33687846-T-C

Variant summary

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

The NM_001281956.2(CSMD2):c.4052+5084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,870 control chromosomes in the GnomAD database, including 29,400 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 (29400 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD2	NM_001281956.2	c.4052+5084A>G		intron_variant		ENST00000373381.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD2	ENST00000373381.9	c.4052+5084A>G		intron_variant		1	NM_001281956.2	P2
CSMD2	ENST00000373388.7	c.3932+5084A>G		intron_variant		1
CSMD2	ENST00000619121.4	c.3932+5084A>G		intron_variant		5		A2
CSMD2	ENST00000373380.5	n.892+5084A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94031 AN: 151752 Hom.: 29385 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.620 AC: 94090 AN: 151870 Hom.: 29400 Cov.: 32 AF XY: 0.620 AC XY: 46014 AN XY: 74188

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.630

Alfa AF: 0.538 Hom.: 1748

Bravo AF: 0.614

Asia WGS AF: 0.618 AC: 2147 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.064
Dann	Benign	0.73

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: rs1036756; hg19: chr1-34153446;