chr2-205396305-G-A

Variant names:

• chr2-205396305-G-A
• rs849230
• NM_001302769.2:c.2631-4708G>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.2631-4708G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,300 control chromosomes in the GnomAD database, including 59,070 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 0.88 (59070 hom., cov: 34)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	NM_001302769.2	MANE Select	c.2631-4708G>A		intron	N/A	NP_001289698.1
	PARD3B	NM_152526.6		c.2445-4708G>A		intron	N/A	NP_689739.4
	PARD3B	NM_057177.7		c.2424-4708G>A		intron	N/A	NP_476518.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3B	ENST00000406610.7	TSL:1 MANE Select	c.2631-4708G>A		intron	N/A	ENSP00000385848.2
	PARD3B	ENST00000358768.6	TSL:1	c.2445-4708G>A		intron	N/A	ENSP00000351618.2
	PARD3B	ENST00000351153.5	TSL:1	c.2424-4708G>A		intron	N/A	ENSP00000317261.2

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133517 AN: 152182 Hom.: 59048 Cov.: 34

Gnomad AFR AF: 0.753

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.877 AC: 133585 AN: 152300 Hom.: 59070 Cov.: 34 AF XY: 0.880 AC XY: 65569 AN XY: 74470

African (AFR) AF: 0.752 AC: 31259 AN: 41546

American (AMR) AF: 0.928 AC: 14199 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3213 AN: 3472

East Asian (EAS) AF: 0.969 AC: 5020 AN: 5182

South Asian (SAS) AF: 0.934 AC: 4507 AN: 4824

European-Finnish (FIN) AF: 0.956 AC: 10157 AN: 10620

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62183 AN: 68034

Other (OTH) AF: 0.881 AC: 1865 AN: 2116

Alfa AF: 0.910 Hom.: 29257

Bravo AF: 0.872

Asia WGS AF: 0.939 AC: 3265 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.64
PhyloP100		1.7
Mutation Taster		=100/0	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: rs849230; hg19: chr2-206261029;