NM_001281956.2:c.518-22838A>G

Variant names:

• chr1-33958792-T-C
• rs549048
• NM_001281956.2:c.518-22838A>G

Variant summary

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

The NM_001281956.2(CSMD2):​c.518-22838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,032 control chromosomes in the GnomAD database, including 25,627 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 0.57 (25627 hom., cov: 32)
• Consequence: CSMD2 NM_001281956.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD2	NM_001281956.2	c.518-22838A>G		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.518-22838A>G		intron_variant	Intron 3 of 70	1	NM_001281956.2	ENSP00000362479.4
CSMD2	ENST00000373388.7	c.398-22838A>G		intron_variant	Intron 3 of 69	1		ENSP00000362486.3
CSMD2	ENST00000619121.4	c.398-22838A>G		intron_variant	Intron 3 of 70	5		ENSP00000483463.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87113 AN: 151914 Hom.: 25588 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.574 AC: 87200 AN: 152032 Hom.: 25627 Cov.: 32 AF XY: 0.566 AC XY: 42032 AN XY: 74292

African (AFR) AF: 0.707 AC: 29324 AN: 41468

American (AMR) AF: 0.468 AC: 7150 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2378 AN: 5164

South Asian (SAS) AF: 0.481 AC: 2321 AN: 4822

European-Finnish (FIN) AF: 0.515 AC: 5439 AN: 10558

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36684 AN: 67968

Other (OTH) AF: 0.567 AC: 1196 AN: 2110

Alfa AF: 0.544 Hom.: 50539

Bravo AF: 0.574

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.35
PhyloP100		-2.2
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: rs549048; hg19: chr1-34424393;