rs10914850

Positions:

• chr1-34030493-T-C

Variant summary

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

The ENST00000373381.9(CSMD2):​c.517+2101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,184 control chromosomes in the GnomAD database, including 1,264 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 0.11 (1264 hom., cov: 32)
• Consequence: CSMD2 ENST00000373381.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.517+2101A>G		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+2101A>G		intron_variant		1	NM_001281956.2	ENSP00000362479	P2
CSMD2	ENST00000373388.7	c.397+2101A>G		intron_variant		1		ENSP00000362486
CSMD2	ENST00000619121.4	c.397+2101A>G		intron_variant		5		ENSP00000483463	A2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16269 AN: 152066 Hom.: 1265 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.107 AC: 16290 AN: 152184 Hom.: 1264 Cov.: 32 AF XY: 0.112 AC XY: 8371 AN XY: 74412

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0735 Hom.: 1329

Bravo AF: 0.115

Asia WGS AF: 0.278 AC: 963 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.48

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: rs10914850; hg19: chr1-34496094;