chr2-169767711-C-A

Variant names:

• chr2-169767711-C-A
• rs2114646

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The variant allele was found at a frequency of 0.000016 in 374,500 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.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PTCHD3P2 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 11 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD3P2		n.169767711C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL23	ENST00000437875.1	c.830-5609C>A		intron_variant	Intron 2 of 2	3		ENSP00000394732.1
KLHL23	ENST00000448589.1	c.44-8730C>A		intron_variant	Intron 1 of 1	2		ENSP00000400833.1
PTCHD3P2	ENST00000424937.1	n.1087+2G>T		splice_donor_variant, intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000225 AC: 5 AN: 222526 Hom.: 0 Cov.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126682

African (AFR) AF: 0.000151 AC: 1 AN: 6624

American (AMR) AF: 0.00 AC: 0 AN: 20828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4650

East Asian (EAS) AF: 0.00 AC: 0 AN: 9912

South Asian (SAS) AF: 0.00 AC: 0 AN: 37526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 120068

Other (OTH) AF: 0.000388 AC: 4 AN: 10314

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74192

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 4612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs2114646; hg19: chr2-170624221;