Variant 3-111884214-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001134438.2(PHLDB2):c.137G>T(p.Ser46Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000805 in 1,614,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 6 hom. )

Consequence

PHLDB2
NM_001134438.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.01

Variant links:

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]

PHLDB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064759552).

BP6

Variant 3-111884214-G-T is Benign according to our data. Variant chr3-111884214-G-T is described in ClinVar as [Benign]. Clinvar id is 775892.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PHLDB2	NM_001134438.2 linkuse as main transcript	c.137G>T	p.Ser46Ile	missense_variant	2/18	ENST00000431670.7
PHLDB2	NM_001134439.2 linkuse as main transcript	c.137G>T	p.Ser46Ile	missense_variant	2/18
PHLDB2	NM_001134437.2 linkuse as main transcript	c.218G>T	p.Ser73Ile	missense_variant	3/18
PHLDB2	NM_145753.2 linkuse as main transcript	c.137G>T	p.Ser46Ile	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDB2	ENST00000431670.7 linkuse as main transcript	c.137G>T	p.Ser46Ile	missense_variant	2/18	1	NM_001134438.2	P3	Q86SQ0-1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

664

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00113

AC:

283

AN:

251068

Hom.:

AF XY:

0.000833

AC XY:

113

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000432

AC:

632

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

264

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0161

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.00439

AC:

668

AN:

152232

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000626

Hom.:

Bravo

AF:

0.00490

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;.;D;D;D;D;.

MetaRNN

Benign

0.0065

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.96

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;N;N;N;D;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D;D;D;D

Polyphen

0.96

D;D;D;.;D;D;D;D

Vest4

0.49

MVP

0.66

MPC

0.35

ClinPred

0.038

GERP RS

5.9

Varity_R

0.47

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over