chr2-169767711-C-T

Position:

• chr2-169767711-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000424937.1(PTCHD3P2):​n.1087+2G>A variant causes a splice donor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 373,276 control chromosomes in the GnomAD database, including 12,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3991 hom., cov: 32)
  • Exomes 𝑓: 0.25 (8798 hom.)
• Consequence: PTCHD3P2 ENST00000424937.1 splice_donor, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

Genes affected

PTCHD3P2 (HGNC:44946): (patched domain containing 3 pseudogene 2)

KLHL23 (HGNC:27506): (kelch like family member 23)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3P2	ENST00000424937.1	n.1087+2G>A		splice_donor_variant, non_coding_transcript_variant
KLHL23	ENST00000437875.1	c.830-5609C>T		intron_variant		3		ENSP00000394732
KLHL23	ENST00000448589.1	c.46-8730C>T		intron_variant		2		ENSP00000400833

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30277 AN: 151926 Hom.: 3979 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.255 AC: 56323 AN: 221232 Hom.: 8798 Cov.: 0 AF XY: 0.252 AC XY: 31720 AN XY: 125936

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.199 AC: 30299 AN: 152044 Hom.: 3991 Cov.: 32 AF XY: 0.208 AC XY: 15456 AN XY: 74300

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.186

Alfa AF: 0.208 Hom.: 3469

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2114646; hg19: chr2-170624221;