1-34011980-A-G

Position:

• chr1-34011980-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.517+20614T>C		intron_variant		ENST00000373381.9	NP_001268885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD2	ENST00000373381.9	c.517+20614T>C		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.397+20614T>C		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.397+20614T>C		intron_variant		5		ENSP00000483463	A2

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

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.162

Alfa AF: 0.110 Hom.: 2776

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

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: rs1325258; hg19: chr1-34477581;