Variant chr11-2929039-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003311.4(PHLDA2):c.326A>G(p.Asp109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PHLDA2
NM_003311.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.391

Variant links:

Genes affected

PHLDA2 (HGNC:12385): (pleckstrin homology like domain family A member 2) This gene is located in a cluster of imprinted genes on chromosome 11p15.5, which is considered to be an important tumor suppressor gene region. Alterations in this region may be associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene has been shown to be imprinted, with preferential expression from the maternal allele in placenta and liver. [provided by RefSeq, Oct 2010]

PHLDA2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04546714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDA2	NM_003311.4 linkuse as main transcript	c.326A>G	p.Asp109Gly	missense_variant	1/2	ENST00000314222.5	NP_003302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDA2	ENST00000314222.5 linkuse as main transcript	c.326A>G	p.Asp109Gly	missense_variant	1/2	1	NM_003311.4	ENSP00000319231	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000871

AC:

AN:

229586

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1448310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000766

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.326A>G (p.D109G) alteration is located in exon 1 (coding exon 1) of the PHLDA2 gene. This alteration results from a A to G substitution at nucleotide position 326, causing the aspartic acid (D) at amino acid position 109 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.17

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.85

L;L

MutationTaster

Benign

0.54

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.12

Sift

Benign

0.46

T;.

Sift4G

Benign

0.39

T;.

Polyphen

0.0010

B;B

Vest4

0.073

MutPred

0.21

Gain of MoRF binding (P = 0.0587);Gain of MoRF binding (P = 0.0587);

MVP

0.41

MPC

1.1

ClinPred

0.033

GERP RS

-2.5

Varity_R

0.060

gMVP

0.66

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