Variant chr3-127629284-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015720.4(PODXL2):c.65T>G(p.Val22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000755 in 1,006,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

PODXL2
NM_015720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469

Variant links:

Genes affected

PODXL2 (HGNC:17936): (podocalyxin like 2) This gene is a member of the CD34 family of cell surface transmembrane proteins, which are characterized by an N-terminal extracellular mucin domain, globular and stalk domains, a single pass transmembrane region, and a charged cytoplasmic tail. The encoded protein is a ligand for vascular selectins. [provided by RefSeq, Oct 2012]

PODXL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043830454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODXL2	NM_015720.4 linkuse as main transcript	c.65T>G	p.Val22Gly	missense_variant	1/8	ENST00000342480.7	NP_056535.1	Q9NZ53-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODXL2	ENST00000342480.7 linkuse as main transcript	c.65T>G	p.Val22Gly	missense_variant	1/8	1	NM_015720.4	ENSP00000345359.6		Q9NZ53-1

Frequencies

GnomAD3 genomes

AF:

0.000272

AC:

AN:

143134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000780

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000618

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

863486

Hom.:

Cov.:

AF XY:

0.0000398

AC XY:

AN XY:

401630

show subpopulations

Gnomad4 AFR exome

AF:

0.000797

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000549

Gnomad4 NFE exome

AF:

0.0000141

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000279

AC:

AN:

143246

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

AN XY:

69760

show subpopulations

Gnomad4 AFR

AF:

0.000803

Gnomad4 AMR

AF:

0.000274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000618

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.65T>G (p.V22G) alteration is located in exon 1 (coding exon 1) of the PODXL2 gene. This alteration results from a T to G substitution at nucleotide position 65, causing the valine (V) at amino acid position 22 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

Benign

0.046

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.063

M_CAP

Benign

0.0035

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.030

REVEL

Benign

0.023

Sift

Benign

0.39

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.27

MVP

0.043

MPC

0.26

ClinPred

0.017

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.062

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over