chr2-205198574-G-A

Variant names:

• chr2-205198574-G-A
• rs11681930
• NM_001302769.2:c.2140+5254G>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.2140+5254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,014 control chromosomes in the GnomAD database, including 5,017 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 0.25 (5017 hom., cov: 32)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 8 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.2140+5254G>A		intron_variant	Intron 15 of 22	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.2140+5254G>A		intron_variant	Intron 15 of 22	1	NM_001302769.2	ENSP00000385848.2
PARD3B	ENST00000358768.6	c.1954+5254G>A		intron_variant	Intron 14 of 21	1		ENSP00000351618.2
PARD3B	ENST00000351153.5	c.2140+5254G>A		intron_variant	Intron 15 of 21	1		ENSP00000317261.2
PARD3B	ENST00000349953.7	c.2140+5254G>A		intron_variant	Intron 15 of 21	1		ENSP00000340280.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37538 AN: 151896 Hom.: 5003 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.247 AC: 37585 AN: 152014 Hom.: 5017 Cov.: 32 AF XY: 0.246 AC XY: 18268 AN XY: 74278

African (AFR) AF: 0.331 AC: 13727 AN: 41468

American (AMR) AF: 0.172 AC: 2617 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1721 AN: 5152

South Asian (SAS) AF: 0.207 AC: 994 AN: 4806

European-Finnish (FIN) AF: 0.267 AC: 2814 AN: 10544

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14396 AN: 67998

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.221 Hom.: 11725

Bravo AF: 0.244

Asia WGS AF: 0.237 AC: 825 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.34
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11681930; hg19: chr2-206063298;