rs899378

Variant names:

• chr1-34049729-C-T
• rs899378
• NM_001281956.2:c.405-17023G>A

Variant summary

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

The NM_001281956.2(CSMD2):​c.405-17023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,014 control chromosomes in the GnomAD database, including 20,713 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 0.51 (20713 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.405-17023G>A		intron_variant	Intron 2 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.405-17023G>A		intron_variant	Intron 2 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.285-17023G>A		intron_variant	Intron 2 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.285-17023G>A		intron_variant	Intron 2 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77245 AN: 151894 Hom.: 20705 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.508 AC: 77269 AN: 152014 Hom.: 20713 Cov.: 32 AF XY: 0.505 AC XY: 37505 AN XY: 74308

African (AFR) AF: 0.372 AC: 15430 AN: 41466

American (AMR) AF: 0.470 AC: 7183 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1612 AN: 3454

East Asian (EAS) AF: 0.272 AC: 1401 AN: 5152

South Asian (SAS) AF: 0.396 AC: 1910 AN: 4818

European-Finnish (FIN) AF: 0.643 AC: 6794 AN: 10562

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41252 AN: 67982

Other (OTH) AF: 0.514 AC: 1084 AN: 2108

Alfa AF: 0.568 Hom.: 96795

Bravo AF: 0.492

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.46
PhyloP100		-1.8
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: rs899378; hg19: chr1-34515330;