2-205440432-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302769.2(PARD3B):c.2804C>T(p.Thr935Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,613,938 control chromosomes in the GnomAD database, including 4,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (886 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3426 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017732084).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3B	NM_001302769.2	c.2804C>T	p.Thr935Ile	missense_variant	20/23	ENST00000406610.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3B	ENST00000406610.7	c.2804C>T	p.Thr935Ile	missense_variant	20/23	1	NM_001302769.2	P1

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14067 AN: 152084 Hom.: 883 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0848

GnomAD3 exomes AF: 0.0569 AC: 14179 AN: 249212 Hom.: 618 AF XY: 0.0541 AC XY: 7319 AN XY: 135202

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.0460

Gnomad ASJ exome AF: 0.0763

Gnomad EAS exome AF: 0.000279

Gnomad SAS exome AF: 0.0184

Gnomad FIN exome AF: 0.0436

Gnomad NFE exome AF: 0.0623

Gnomad OTH exome AF: 0.0597

GnomAD4 exome AF: 0.0630 AC: 92157 AN: 1461736 Hom.: 3426 Cov.: 32 AF XY: 0.0613 AC XY: 44593 AN XY: 727166

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0496

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0188

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.0660

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.0925 AC: 14085 AN: 152202 Hom.: 886 Cov.: 32 AF XY: 0.0884 AC XY: 6579 AN XY: 74412

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0197

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0645 Hom.: 896

Bravo AF: 0.0988

TwinsUK AF: 0.0655 AC: 243

ALSPAC AF: 0.0675 AC: 260

ESP6500AA AF: 0.176 AC: 693

ESP6500EA AF: 0.0688 AC: 572

ExAC AF: 0.0582 AC: 7031

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.0697

EpiControl AF: 0.0689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	20
Dann	Benign	0.077
DEOGEN2	Benign	0.00060	T;.;.;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.70	T;T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.19	N;N;N;.;.
REVEL	Benign	0.089
Sift	Benign	0.43	T;T;T;.;.
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.051	B;B;.;.;.
Vest4		0.056
MPC		0.023
ClinPred		0.0079	T
GERP RS		4.4
Varity_R		0.045
gMVP		0.15

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

Other links and lift over

dbSNP: rs10185378; hg19: chr2-206305156; COSMIC: COSV62509457;