rs10511302

Positions:

• chr3-111968909-T-C

Variant summary

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

The NM_001134438.2(PHLDB2):​c.3316-781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,040 control chromosomes in the GnomAD database, including 12,114 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 0.39 (12114 hom., cov: 32)
• Consequence: PHLDB2 NM_001134438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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 = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.3316-781T>C		intron_variant		ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134437.2	c.3268-781T>C		intron_variant			NP_001127909.1
PHLDB2	NM_001134439.2	c.3316-781T>C		intron_variant			NP_001127911.1
PHLDB2	NM_145753.2	c.3187-781T>C		intron_variant			NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.3316-781T>C		intron_variant		1	NM_001134438.2	ENSP00000405405	P3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59250 AN: 151922 Hom.: 12116 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.390 AC: 59246 AN: 152040 Hom.: 12114 Cov.: 32 AF XY: 0.393 AC XY: 29239 AN XY: 74324

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.432

Alfa AF: 0.426 Hom.: 28416

Bravo AF: 0.391

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.43

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: rs10511302; hg19: chr3-111687756;