Variant 3-191461439-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001083308.1(PYDC2):c.277G>A(p.Val93Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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: 0.0000048 ( 0 hom. )

Consequence

PYDC2
NM_001083308.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.252

Variant links:

Genes affected

PYDC2 (HGNC:33512): (pyrin domain containing 2) Involved in several processes, including negative regulation of NLRP3 inflammasome complex assembly; negative regulation of signal transduction; and regulation of gene expression. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PYDC2 links:

PYDC2-AS1 (HGNC:52874): (PYDC2 antisense RNA 1)

PYDC2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057829916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYDC2	NM_001083308.1 linkuse as main transcript	c.277G>A	p.Val93Met	missense_variant	1/1	ENST00000518817.1	NP_001076777.1
PYDC2-AS1	NR_120606.1 linkuse as main transcript	n.81+35835G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYDC2	ENST00000518817.1 linkuse as main transcript	c.277G>A	p.Val93Met	missense_variant	1/1		NM_001083308.1	ENSP00000492367	P1
PYDC2-AS1	ENST00000641158.1 linkuse as main transcript	n.79+35835G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246694

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000389

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460852

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000413

AC:

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

Sep 23, 2023

The c.277G>A (p.V93M) alteration is located in exon 1 (coding exon 1) of the PYDC2 gene. This alteration results from a G to A substitution at nucleotide position 277, causing the valine (V) at amino acid position 93 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.4

DANN

Benign

0.97

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.35

M_CAP

Benign

0.0029

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

REVEL

Benign

0.16

Sift4G

Pathogenic

0.0

Polyphen

0.93

Vest4

0.12

MutPred

0.13

Gain of disorder (P = 0.0711);

MVP

0.10

MPC

0.12

ClinPred

0.041

GERP RS

0.16

Varity_R

0.074

gMVP

0.030

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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