chr1-33519561-C-G

Position:

• chr1-33519561-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001281956.2(CSMD2):​c.10853G>C​(p.Ser3618Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSMD2 NM_001281956.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02002126).
• BP6: Variant 1-33519561-C-G is Benign according to our data. Variant chr1-33519561-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2539097.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD2	NM_001281956.2	c.10853G>C	p.Ser3618Thr	missense_variant	70/71	ENST00000373381.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD2	ENST00000373381.9	c.10853G>C	p.Ser3618Thr	missense_variant	70/71	1	NM_001281956.2	P2
CSMD2	ENST00000373388.7	c.10421G>C	p.Ser3474Thr	missense_variant	69/70	1
CSMD2	ENST00000619121.4	c.10733G>C	p.Ser3578Thr	missense_variant	70/71	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.8
DANN	Benign	0.79
DEOGEN2	Benign	0.014	.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.020	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	.;N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.81	N;.;.
REVEL	Benign	0.063
Sift	Benign	0.86	T;.;.
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.10
MutPred		0.18		.;Loss of disorder (P = 0.1631);.;
MVP		0.072
ClinPred		0.041	T
GERP RS		-2.1
Varity_R		0.042
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-33985161;