rs712507

Positions:

• chr3-111936542-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.2131-2933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,112 control chromosomes in the GnomAD database, including 36,412 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 0.69 (36412 hom., cov: 33)
• Consequence: PHLDB2 NM_001134438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.2131-2933T>C		intron_variant		ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134437.2	c.2083-2933T>C		intron_variant			NP_001127909.1
PHLDB2	NM_001134439.2	c.2131-2933T>C		intron_variant			NP_001127911.1
PHLDB2	NM_145753.2	c.2002-2933T>C		intron_variant			NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.2131-2933T>C		intron_variant		1	NM_001134438.2	ENSP00000405405	P3

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104631 AN: 151994 Hom.: 36372 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.688 AC: 104719 AN: 152112 Hom.: 36412 Cov.: 33 AF XY: 0.689 AC XY: 51234 AN XY: 74400

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.671

Alfa AF: 0.659 Hom.: 15135

Bravo AF: 0.695

Asia WGS AF: 0.814 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.59

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: rs712507; hg19: chr3-111655389;