15-93024544-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001271.4(CHD2):c.5326C>T(p.Pro1776Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1776A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHD2 NM_001271.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CHD2
• BP4: Computational evidence support a benign effect (MetaRNN=0.18823385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.5326C>T	p.Pro1776Ser	missense_variant	39/39	ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.5326C>T	p.Pro1776Ser	missense_variant	39/39	5	NM_001271.4	P1
CHD2	ENST00000625662.3	c.*1497C>T		3_prime_UTR_variant, NMD_transcript_variant	35/35	5
CHD2	ENST00000627460.1	c.*458C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249578 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135408

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.90	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.16	T
Sift4G	Benign	0.33	T
Polyphen		0.63	P
Vest4		0.21
MVP		0.63
MPC		0.90
ClinPred		0.59	D
GERP RS		5.6
Varity_R		0.074
gMVP		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371006816; hg19: chr15-93567774;