2-205104496-G-A

Variant names:

• chr2-205104496-G-A
• rs2289025
• NM_001302769.2:c.575G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302769.2(PARD3B):​c.575G>A​(p.Arg192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,565,804 control chromosomes in the GnomAD database, including 311,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.61 (28369 hom., cov: 32)
  • Exomes 𝑓: 0.63 (282777 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 34 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=1.5535625E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302769.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	NM_001302769.2	MANE Select	c.575G>A	p.Arg192Lys	missense	Exon 5 of 23	NP_001289698.1	Q8TEW8-1
	PARD3B	NM_152526.6		c.575G>A	p.Arg192Lys	missense	Exon 5 of 22	NP_689739.4
	PARD3B	NM_057177.7		c.575G>A	p.Arg192Lys	missense	Exon 5 of 22	NP_476518.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	ENST00000406610.7	TSL:1 MANE Select	c.575G>A	p.Arg192Lys	missense	Exon 5 of 23	ENSP00000385848.2	Q8TEW8-1
	PARD3B	ENST00000358768.6	TSL:1	c.575G>A	p.Arg192Lys	missense	Exon 5 of 22	ENSP00000351618.2	Q8TEW8-2
	PARD3B	ENST00000351153.5	TSL:1	c.575G>A	p.Arg192Lys	missense	Exon 5 of 22	ENSP00000317261.2	Q8TEW8-6

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91963 AN: 151894 Hom.: 28342 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.611

GnomAD2 exomes AF: 0.650 AC: 161777 AN: 248738 AF XY: 0.650

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.791

Gnomad FIN exome AF: 0.556

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.622

GnomAD4 exome AF: 0.629 AC: 889855 AN: 1413792 Hom.: 282777 Cov.: 31 AF XY: 0.631 AC XY: 445481 AN XY: 705864

African (AFR) AF: 0.520 AC: 16835 AN: 32396

American (AMR) AF: 0.756 AC: 33717 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 14260 AN: 25866

East Asian (EAS) AF: 0.804 AC: 31645 AN: 39380

South Asian (SAS) AF: 0.714 AC: 60730 AN: 85096

European-Finnish (FIN) AF: 0.554 AC: 29451 AN: 53158

Middle Eastern (MID) AF: 0.606 AC: 3443 AN: 5684

European-Non Finnish (NFE) AF: 0.620 AC: 663042 AN: 1068890

Other (OTH) AF: 0.625 AC: 36732 AN: 58750

GnomAD4 genome AF: 0.605 AC: 92039 AN: 152012 Hom.: 28369 Cov.: 32 AF XY: 0.611 AC XY: 45407 AN XY: 74318

African (AFR) AF: 0.523 AC: 21684 AN: 41444

American (AMR) AF: 0.699 AC: 10677 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1914 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4113 AN: 5160

South Asian (SAS) AF: 0.721 AC: 3471 AN: 4812

European-Finnish (FIN) AF: 0.569 AC: 6006 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42162 AN: 67960

Other (OTH) AF: 0.614 AC: 1296 AN: 2110

Alfa AF: 0.620 Hom.: 131930

Bravo AF: 0.613

TwinsUK AF: 0.632 AC: 2344

ALSPAC AF: 0.624 AC: 2403

ESP6500AA AF: 0.543 AC: 1988

ESP6500EA AF: 0.624 AC: 5112

ExAC AF: 0.644 AC: 77746

Asia WGS AF: 0.753 AC: 2621 AN: 3478

EpiCase AF: 0.624

EpiControl AF: 0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.48
DEOGEN2	Benign	0.00057	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00045	N
LIST_S2	Benign	0.039	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.85	N
PhyloP100		0.25
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.045
MPC		0.022
ClinPred		0.0014	T
GERP RS		0.10
Varity_R		0.042
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2289025; hg19: chr2-205969220; COSMIC: COSV107412479;