Genetic Variant PTCHD3P2:n.169767711C>G (chr2-169767711-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The variant allele was found at a frequency of 0.000018 in 222,526 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: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PTCHD3P2
intragenic

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

11 publications found

Variant links:

Genes affected

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

PTCHD3P2 links:

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

KLHL23 links:

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ACMG classification

Classification was made for transcript

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=-0.66).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
KLHL23	ENST00000437875.1 link	c.830-5609C>G	intron_variant	Intron 2 of 2	3	ENSP00000394732.1	H7C0F4
KLHL23	ENST00000448589.1 link	c.44-8730C>G	intron_variant	Intron 1 of 1	2	ENSP00000400833.1	H7C1K9
PTCHD3P2	ENST00000424937.1 link	n.1087+2G>C	splice_donor_variant, intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000180

AC:

AN:

222526

Hom.:

Cov.:

AF XY:

0.00000789

AC XY:

AN XY:

126682

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6624

American (AMR)

AF:

0.0000480

AC:

AN:

20828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4650

East Asian (EAS)

AF:

0.00

AC:

AN:

9912

South Asian (SAS)

AF:

0.00

AC:

AN:

37526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1964

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

120068

Other (OTH)

AF:

0.00

AC:

AN:

10314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0310196), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

-0.66

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.30

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over