chr11-2929246-G-C

Position:

• chr11-2929246-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003311.4(PHLDA2):​c.119C>G​(p.Pro40Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHLDA2 NM_003311.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24862027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDA2	NM_003311.4	c.119C>G	p.Pro40Arg	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	c.119C>G	p.Pro40Arg	missense_variant	1/2	1	NM_003311.4	ENSP00000319231	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.119C>G (p.P40R) alteration is located in exon 1 (coding exon 1) of the PHLDA2 gene. This alteration results from a C to G substitution at nucleotide position 119, causing the proline (P) at amino acid position 40 to be replaced by an arginine (R). 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	Pathogenic	0.56
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.74	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.3	D;.
REVEL	Benign	0.060
Sift	Benign	0.20	T;.
Sift4G	Uncertain	0.032	D;.
Polyphen		0.22	B;B
Vest4		0.16
MutPred		0.37		Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);
MVP		0.56
MPC		0.99
ClinPred		0.68	D
GERP RS		3.5
Varity_R		0.32
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-2950476;