15-92901239-T-C

Variant names:

• chr15-92901239-T-C
• rs193920953
• NM_001271.4:c.2T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting 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 Uncertain_significance. Variant got 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 2 codons. Genomic position: 92901241. Lost 0.001 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.2T>C	p.Met1?	start_lost	Exon 2 of 39	ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3	c.2T>C	p.Met1?	start_lost	Exon 2 of 13		NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.2T>C	p.Met1?	start_lost	Exon 2 of 39	5	NM_001271.4	ENSP00000377747.4

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

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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
DEOGEN2	Benign	0.058	.;.;T;.;.;T;.
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
PROVEAN	Benign	-0.11	.;.;N;.;.;.;N
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	.;.;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;