rs1325258

Variant names:

• chr1-34011980-A-G
• rs1325258
• NM_001281956.2:c.517+20614T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-34011980-A-G
• chr1-34011980-A-T

Variant summary

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

The NM_001281956.2(CSMD2):​c.517+20614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,196 control chromosomes in the GnomAD database, including 2,349 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 0.15 (2349 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.517+20614T>C		intron_variant	Intron 3 of 70	ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.517+20614T>C		intron_variant	Intron 3 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.397+20614T>C		intron_variant	Intron 3 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.397+20614T>C		intron_variant	Intron 3 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22952 AN: 152078 Hom.: 2337 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.151 AC: 23019 AN: 152196 Hom.: 2349 Cov.: 32 AF XY: 0.157 AC XY: 11687 AN XY: 74404

African (AFR) AF: 0.184 AC: 7648 AN: 41518

American (AMR) AF: 0.219 AC: 3355 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 309 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2361 AN: 5156

South Asian (SAS) AF: 0.348 AC: 1677 AN: 4824

European-Finnish (FIN) AF: 0.0917 AC: 973 AN: 10610

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6236 AN: 68016

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.116 Hom.: 6011

Bravo AF: 0.161

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		0.065
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: rs1325258; hg19: chr1-34477581;