Variant chr5-134910454-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032151.5(PCBD2):c.204C>G(p.His68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCBD2
NM_032151.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

PCBD2 (HGNC:24474): (pterin-4 alpha-carbinolamine dehydratase 2) Predicted to enable 4-alpha-hydroxytetrahydrobiopterin dehydratase activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PCBD2 links:

PCBD2 (HGNC:):

PCBD2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24193943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBD2	NM_032151.5 linkuse as main transcript	c.204C>G	p.His68Gln	missense_variant	2/4	ENST00000254908.11	NP_115527.3	Q9H0N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCBD2	ENST00000254908.11 linkuse as main transcript	c.204C>G	p.His68Gln	missense_variant	2/4	1	NM_032151.5	ENSP00000254908.6	Q9H0N5
PCBD2	ENST00000512783.5 linkuse as main transcript	c.204C>G	p.His68Gln	missense_variant	2/5	1		ENSP00000421544.1	Q9H0N5
PCBD2	ENST00000504352.1 linkuse as main transcript	n.171C>G		non_coding_transcript_exon_variant	2/8	5		ENSP00000426161.1	H0YA52
PCBD2	ENST00000510013.1 linkuse as main transcript	n.293C>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727188

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2023

The c.204C>G (p.H68Q) alteration is located in exon 2 (coding exon 2) of the PCBD2 gene. This alteration results from a C to G substitution at nucleotide position 204, causing the histidine (H) at amino acid position 68 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

-0.20

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.7

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.072

T;T

Sift4G

Benign

0.076

T;T

Polyphen

0.0020

B;B

Vest4

0.13

MutPred

0.32

Loss of catalytic residue at N69 (P = 0.0447);Loss of catalytic residue at N69 (P = 0.0447);

MVP

0.76

MPC

0.21

ClinPred

0.72

GERP RS

4.5

Varity_R

0.12

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over