rs2252655

Positions:

• chr10-34416631-A-G
• chr10-34416631-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184785.2(PARD3):​c.715-14714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,010 control chromosomes in the GnomAD database, including 26,128 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 (26128 hom., cov: 32)
• Consequence: PARD3 NM_001184785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3	NM_001184785.2	c.715-14714T>C		intron_variant		ENST00000374788.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3	ENST00000374788.8	c.715-14714T>C		intron_variant		1	NM_001184785.2	A1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83472 AN: 151892 Hom.: 26070 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.550 AC: 83587 AN: 152010 Hom.: 26128 Cov.: 32 AF XY: 0.549 AC XY: 40758 AN XY: 74296

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.503

Alfa AF: 0.427 Hom.: 19832

Bravo AF: 0.567

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.80

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: rs2252655; hg19: chr10-34705559; COSMIC: COSV60749226;