15-92997085-GA-GAAA

Variant names:

• chr15-92997085-G-GAA
• ENST00000394196.9:c.3722_3723dupAA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1 BS2

The NM_001271.4(CHD2):​c.3733_3734dupAA variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,315,774 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: CHD2 NM_001271.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.89

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 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.3733_3734dupAA		splice_donor_variant, intron_variant	Intron 29 of 38	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.3722_3723dupAA	p.Glu1242AsnfsTer4	frameshift_variant	Exon 29 of 39	5	NM_001271.4	ENSP00000377747.4
CHD2	ENST00000637789.1	n.*297_*298dupAA		non_coding_transcript_exon_variant	Exon 6 of 9	5		ENSP00000489767.1
CHD2	ENST00000637789.1	n.*297_*298dupAA		3_prime_UTR_variant	Exon 6 of 9	5		ENSP00000489767.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000456 AC: 6 AN: 1315774 Hom.: 0 Cov.: 32 AF XY: 0.00000306 AC XY: 2 AN XY: 653466

Gnomad4 AFR exome AF: 0.0000349

Gnomad4 AMR exome AF: 0.0000874

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000138

Gnomad4 FIN exome AF: 0.0000208

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr15-93540315;