Variant chr21-37267290-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006052.2(VPS26C):c.5G>A(p.Gly2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VPS26C
NM_006052.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

VPS26C (HGNC:3044): (VPS26 endosomal protein sorting factor C) The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and cognitive disability. The DSCR3 (Down syndrome critical region gene 3) gene is found in this region and is predictated to contain eight exons. DSCR3 is expressed in most tissues examined. [provided by RefSeq, Jul 2008]

VPS26C links:

VPS26C (HGNC:):

VPS26C links:

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ACMG classification

Classification made for transcript

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=0.22863448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS26C	NM_006052.2 linkuse as main transcript	c.5G>A	p.Gly2Glu	missense_variant	1/8	ENST00000309117.11	NP_006043.1	O14972-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS26C	ENST00000309117.11 linkuse as main transcript	c.5G>A	p.Gly2Glu	missense_variant	1/8	1	NM_006052.2	ENSP00000311399.6		O14972-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245782

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133470

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442854

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717986

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

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

Jan 10, 2023

The c.5G>A (p.G2E) alteration is located in exon 1 (coding exon 1) of the DSCR3 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the glycine (G) at amino acid position 2 to be replaced by a glutamic acid (E). 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

0.73

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

D;D;D;D;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.99

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.049

D;D;D;D

Sift4G

Uncertain

0.041

D;T;D;T

Polyphen

0.89

.;P;.;.

Vest4

0.34

MutPred

0.58

Loss of MoRF binding (P = 0.0277);Loss of MoRF binding (P = 0.0277);Loss of MoRF binding (P = 0.0277);Loss of MoRF binding (P = 0.0277);

MVP

0.29

MPC

0.66

ClinPred

0.29

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.28

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

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