2-204616144-T-C

Variant names:

• chr2-204616144-T-C
• rs12621708
• NM_001302769.2:c.120+70025T>C

Variant summary

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

The NM_001302769.2(PARD3B):​c.120+70025T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,104 control chromosomes in the GnomAD database, including 26,563 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 0.55 (26563 hom., cov: 33)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.120+70025T>C		intron_variant	Intron 1 of 22	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.120+70025T>C		intron_variant	Intron 1 of 22	1	NM_001302769.2	ENSP00000385848.2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84272 AN: 151986 Hom.: 26562 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.554 AC: 84289 AN: 152104 Hom.: 26563 Cov.: 33 AF XY: 0.554 AC XY: 41174 AN XY: 74342

African (AFR) AF: 0.231 AC: 9572 AN: 41522

American (AMR) AF: 0.673 AC: 10270 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2955 AN: 5144

South Asian (SAS) AF: 0.502 AC: 2423 AN: 4826

European-Finnish (FIN) AF: 0.702 AC: 7434 AN: 10584

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47314 AN: 67978

Other (OTH) AF: 0.605 AC: 1278 AN: 2112

Alfa AF: 0.656 Hom.: 141084

Bravo AF: 0.543

Asia WGS AF: 0.509 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		0.73
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: rs12621708; hg19: chr2-205480867;