1-33526770-T-G

Variant names:

• chr1-33526770-T-G
• rs2794593
• NM_001281956.2:c.10234+426A>C

Variant summary

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

The NM_001281956.2(CSMD2):​c.10234+426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,116 control chromosomes in the GnomAD database, including 36,048 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 0.69 (36048 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.10234+426A>C		intron_variant	Intron 65 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.10234+426A>C		intron_variant	Intron 65 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.9802+426A>C		intron_variant	Intron 64 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.10114+426A>C		intron_variant	Intron 65 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104397 AN: 151998 Hom.: 36030 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.687 AC: 104457 AN: 152116 Hom.: 36048 Cov.: 32 AF XY: 0.682 AC XY: 50684 AN XY: 74346

African (AFR) AF: 0.739 AC: 30660 AN: 41496

American (AMR) AF: 0.576 AC: 8802 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3756 AN: 5172

South Asian (SAS) AF: 0.646 AC: 3120 AN: 4828

European-Finnish (FIN) AF: 0.663 AC: 6993 AN: 10554

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46521 AN: 67988

Other (OTH) AF: 0.711 AC: 1502 AN: 2114

Alfa AF: 0.676 Hom.: 58361

Bravo AF: 0.683

Asia WGS AF: 0.697 AC: 2426 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	4.5
DANN	Benign	0.62
PhyloP100		0.87
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: rs2794593; hg19: chr1-33992370;