2-205440432-C-T

Variant names:

• chr2-205440432-C-T
• rs10185378
• NM_001302769.2:c.2804C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.2804C>T	p.Thr935Ile	missense_variant	Exon 20 of 23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.2804C>T	p.Thr935Ile	missense_variant	Exon 20 of 23	1	NM_001302769.2	ENSP00000385848.2

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

GnomAD2 exomes AF: 0.0569 AC: 14179 AN: 249212 AF XY: 0.0541

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 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

African (AFR) AF: 0.188 AC: 6282 AN: 33472

American (AMR) AF: 0.0496 AC: 2218 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 1952 AN: 26134

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39682

South Asian (SAS) AF: 0.0188 AC: 1618 AN: 86254

European-Finnish (FIN) AF: 0.0417 AC: 2229 AN: 53420

Middle Eastern (MID) AF: 0.0676 AC: 390 AN: 5766

European-Non Finnish (NFE) AF: 0.0660 AC: 73425 AN: 1111894

Other (OTH) AF: 0.0668 AC: 4034 AN: 60390

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

African (AFR) AF: 0.180 AC: 7482 AN: 41520

American (AMR) AF: 0.0754 AC: 1152 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4818

European-Finnish (FIN) AF: 0.0462 AC: 489 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0631 AC: 4289 AN: 68020

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.0691 Hom.: 1463

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;.;.;.;.
PhyloP100		1.8
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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