rs2276677

Positions:

• chr2-205125306-C-A
• chr2-205125306-C-G
• chr2-205125306-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.1306-303C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,004 control chromosomes in the GnomAD database, including 31,515 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31515 hom., cov: 32)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.1306-303C>A		intron_variant		ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.1306-303C>A		intron_variant		1	NM_001302769.2	ENSP00000385848	P1
PARD3B	ENST00000349953.7	c.1306-303C>A		intron_variant		1		ENSP00000340280
PARD3B	ENST00000351153.5	c.1306-303C>A		intron_variant		1		ENSP00000317261
PARD3B	ENST00000358768.6	c.1306-303C>A		intron_variant		1		ENSP00000351618

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97317 AN: 151888 Hom.: 31487 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.641 AC: 97399 AN: 152004 Hom.: 31515 Cov.: 32 AF XY: 0.645 AC XY: 47939 AN XY: 74302

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.647

Alfa AF: 0.639 Hom.: 51067

Bravo AF: 0.649

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.57

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: rs2276677; hg19: chr2-205990030;