10-110881398-A-G

Position:

• chr10-110881398-A-G

Variant summary

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

The NM_014456.5(PDCD4):​c.209A>G​(p.Asp70Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD4 NM_014456.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.25

Genes affected

PDCD4 (HGNC:8763): (programmed cell death 4) This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

PDCD4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD4	NM_014456.5	c.209A>G	p.Asp70Gly	missense_variant	3/12	ENST00000280154.12	NP_055271.2
PDCD4	NM_145341.4	c.176A>G	p.Asp59Gly	missense_variant	4/13		NP_663314.1
PDCD4	NM_001199492.2	c.167A>G	p.Asp56Gly	missense_variant	3/12		NP_001186421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12	c.209A>G	p.Asp70Gly	missense_variant	3/12	1	NM_014456.5	ENSP00000280154.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Aug 05, 2024

The c.209A>G (p.D70G) alteration is located in exon 3 (coding exon 2) of the PDCD4 gene. This alteration results from a A to G substitution at nucleotide position 209, causing the aspartic acid (D) at amino acid position 70 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.064	T;T;T
Sift4G	Benign	0.17	T;D;T
Polyphen		0.99	.;D;.
Vest4		0.69
MutPred		0.43		.;Gain of methylation at R69 (P = 0.0287);.;
MVP		0.51
MPC		0.47
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.33
gMVP		0.43

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: chr10-112641156;