rs1207421

Variant names:

• chr2-205285870-A-G
• rs1207421
• NM_001302769.2:c.2186-14660A>G

Variant summary

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

The NM_001302769.2(PARD3B):​c.2186-14660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,190 control chromosomes in the GnomAD database, including 62,633 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 0.91 (62633 hom., cov: 31)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.2186-14660A>G		intron_variant	Intron 16 of 22	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.2186-14660A>G		intron_variant	Intron 16 of 22	1	NM_001302769.2	ENSP00000385848.2
PARD3B	ENST00000358768.6	c.2000-14660A>G		intron_variant	Intron 15 of 21	1		ENSP00000351618.2
PARD3B	ENST00000351153.5	c.2186-15594A>G		intron_variant	Intron 16 of 21	1		ENSP00000317261.2
PARD3B	ENST00000349953.7	c.2186-14660A>G		intron_variant	Intron 16 of 21	1		ENSP00000340280.3

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137752 AN: 152072 Hom.: 62575 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.906 AC: 137867 AN: 152190 Hom.: 62633 Cov.: 31 AF XY: 0.907 AC XY: 67513 AN XY: 74402

African (AFR) AF: 0.917 AC: 38082 AN: 41516

American (AMR) AF: 0.942 AC: 14419 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3166 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3664 AN: 5162

South Asian (SAS) AF: 0.916 AC: 4411 AN: 4816

European-Finnish (FIN) AF: 0.912 AC: 9661 AN: 10598

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61407 AN: 68010

Other (OTH) AF: 0.906 AC: 1907 AN: 2106

Alfa AF: 0.902 Hom.: 208066

Bravo AF: 0.907

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-0.49
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: rs1207421; hg19: chr2-206150594;