rs13390

chr11-2929328-A-Cchr11-2929328-A-Gchr11-2929328-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003311.4(PHLDA2):c.37T>G(p.Leu13Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHLDA2 NM_003311.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLDA2	NM_003311.4	c.37T>G	p.Leu13Val	missense_variant	1/2	ENST00000314222.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDA2	ENST00000314222.5	c.37T>G	p.Leu13Val	missense_variant	1/2	1	NM_003311.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;D
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.00065	P
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.99	D;D
Vest4		0.67
MutPred		0.69		Gain of methylation at K15 (P = 0.0763);Gain of methylation at K15 (P = 0.0763);
MVP		0.77
MPC		1.9
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.48
gMVP		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: rs13390; hg19: chr11-2950558;