rs193920953

chr15-92901239-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001271.4(CHD2):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHD2 NM_001271.4 start_lost
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.38

Genes affected

CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.2T>C	p.Met1?	start_lost	2/39	ENST00000394196.9
CHD2	NM_001042572.3	c.2T>C	p.Met1?	start_lost	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.2T>C	p.Met1?	start_lost	2/39	5	NM_001271.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	24
Dann	Benign	0.97
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.022	T
MutationTaster	Benign	0.98	D;D;D
Sift4G	Pathogenic	0.0	D;T;T;.;.;D;D
Polyphen		0.0080, 0.0050	.;B;B;.;.;.;.
Vest4		0.91, 0.95, 0.88, 0.94, 0.87, 0.95
MutPred		0.98		Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);Gain of phosphorylation at M1 (P = 0.0132);
MVP		0.65
ClinPred		0.74	D
GERP RS		6.0
Varity_R		0.75
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs193920953; hg19: chr15-93444469; COSMIC: COSV59122744; COSMIC: COSV59122744;