Genetic Variant PHLDA2:c.*47G>A (chr11-2928631-C-T) – 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.*47G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 416,194 control chromosomes in the GnomAD database, including 6,810 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 0.15 ( 2085 hom., cov: 33)

Exomes 𝑓: 0.18 ( 4725 hom. )

Consequence

PHLDA2
NM_003311.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Publications

18 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:

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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=-0.64).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDA2	NM_003311.4 link	c.*47G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000314222.5	NP_003302.1	Q53GA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDA2	ENST00000314222.5 link	c.*47G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_003311.4	ENSP00000319231.4		Q53GA4
PHLDA2	ENST00000718435.1 link	c.234G>A	p.Thr78Thr	synonymous_variant	Exon 2 of 2			ENSP00000520820.1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22382

AN:

152098

Hom.:

2084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.181

AC:

47782

AN:

263978

Hom.:

4725

Cov.:

AF XY:

0.181

AC XY:

24225

AN XY:

133734

show subpopulations

African (AFR)

AF:

0.0443

AC:

306

AN:

6902

American (AMR)

AF:

0.155

AC:

1104

AN:

7132

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

1784

AN:

9484

East Asian (EAS)

AF:

0.115

AC:

2538

AN:

22010

South Asian (SAS)

AF:

0.195

AC:

1251

AN:

6400

European-Finnish (FIN)

AF:

0.289

AC:

6222

AN:

21534

Middle Eastern (MID)

AF:

0.173

AC:

246

AN:

1422

European-Non Finnish (NFE)

AF:

0.183

AC:

31314

AN:

171434

Other (OTH)

AF:

0.171

AC:

3017

AN:

17660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1867

3734

5600

7467

9334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22379

AN:

152216

Hom.:

2085

Cov.:

AF XY:

0.153

AC XY:

11416

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0454

AC:

1889

AN:

41578

American (AMR)

AF:

0.143

AC:

2183

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3472

East Asian (EAS)

AF:

0.138

AC:

715

AN:

5166

South Asian (SAS)

AF:

0.205

AC:

986

AN:

4816

European-Finnish (FIN)

AF:

0.297

AC:

3141

AN:

10586

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12358

AN:

67978

Other (OTH)

AF:

0.134

AC:

282

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

945

1890

2836

3781

4726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.167

Hom.:

2810

Bravo

AF:

0.130

Asia WGS

AF:

0.151

AC:

525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.0

(source)

DANN

Benign

0.96

PhyloP100

-0.92

Mutation Taster

=100/0

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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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