Genetic Variant PHLDA2:p.Leu13Leu (chr11-2929328-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003311.4(PHLDA2):c.37T>C(p.Leu13Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.165 in 1,605,924 control chromosomes in the GnomAD database, including 24,347 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 0.13 ( 1637 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22710 hom. )

Consequence

PHLDA2
NM_003311.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.81

Publications

16 publications found

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:

ENSG00000305647 (HGNC:):

ENSG00000305647 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDA2	NM_003311.4 link	c.37T>C	p.Leu13Leu	synonymous_variant	Exon 1 of 2	ENST00000314222.5	NP_003302.1	Q53GA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHLDA2	ENST00000314222.5 link	c.37T>C	p.Leu13Leu	synonymous_variant	Exon 1 of 2	1	NM_003311.4	ENSP00000319231.4	Q53GA4
PHLDA2	ENST00000718435.1 link	c.37T>C	p.Leu13Leu	synonymous_variant	Exon 1 of 2			ENSP00000520820.1
ENSG00000305647	ENST00000812147.1 link	n.87+59A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19858

AN:

151426

Hom.:

1638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.129

AC:

30598

AN:

236816

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.0584

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.000403

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.169

AC:

245174

AN:

1454384

Hom.:

22710

Cov.:

AF XY:

0.166

AC XY:

120290

AN XY:

723426

show subpopulations

African (AFR)

AF:

0.0593

AC:

1956

AN:

32976

American (AMR)

AF:

0.0755

AC:

3337

AN:

44188

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3341

AN:

25952

East Asian (EAS)

AF:

0.000332

AC:

AN:

39156

South Asian (SAS)

AF:

0.0729

AC:

6224

AN:

85378

European-Finnish (FIN)

AF:

0.169

AC:

8654

AN:

51334

Middle Eastern (MID)

AF:

0.120

AC:

688

AN:

5722

European-Non Finnish (NFE)

AF:

0.191

AC:

212040

AN:

1109546

Other (OTH)

AF:

0.148

AC:

8921

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10281

20562

30843

41124

51405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.131

AC:

19855

AN:

151540

Hom.:

1637

Cov.:

AF XY:

0.128

AC XY:

9440

AN XY:

74020

show subpopulations

African (AFR)

AF:

0.0634

AC:

2616

AN:

41268

American (AMR)

AF:

0.102

AC:

1552

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3462

East Asian (EAS)

AF:

0.00117

AC:

AN:

5114

South Asian (SAS)

AF:

0.0608

AC:

291

AN:

4788

European-Finnish (FIN)

AF:

0.166

AC:

1744

AN:

10514

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.189

AC:

12819

AN:

67836

Other (OTH)

AF:

0.121

AC:

255

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

893

1786

2680

3573

4466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.154

Hom.:

1133

Bravo

AF:

0.123

Asia WGS

AF:

0.0370

AC:

131

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

6.8

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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11-2929328-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over