2-204965303-C-G

Variant names:

• chr2-204965303-C-G
• NM_001302769.2:c.374C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001302769.2(PARD3B):​c.374C>G​(p.Thr125Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PARD3B NM_001302769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.374C>G	p.Thr125Ser	missense_variant	Exon 3 of 23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.374C>G	p.Thr125Ser	missense_variant	Exon 3 of 23	1	NM_001302769.2	ENSP00000385848.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461524 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.;.;.;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.0	M;.;M;M;M;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.9	D;.;D;D;D;.;.;.
REVEL	Benign	0.18
Sift	Benign	0.073	T;.;T;D;T;.;.;.
Sift4G	Uncertain	0.010	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;D;.;.;.
Vest4		0.79
MutPred		0.23		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;.;.;
MVP		0.77
MPC		0.047
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-205830026;