Genetic Variant ASCC2:p.Glu726Gly (chr22-29789110-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032204.5(ASCC2):c.2177A>G(p.Glu726Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,184 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

ASCC2
NM_032204.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

ASCC2 (HGNC:24103): (activating signal cointegrator 1 complex subunit 2) Predicted to enable ubiquitin binding activity. Involved in regulation of transcription, DNA-templated; rescue of stalled ribosome; and ribosome-associated ubiquitin-dependent protein catabolic process. Located in nucleus. Part of activating signal cointegrator 1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ASCC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034703195).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC2	NM_032204.5 link	c.2177A>G	p.Glu726Gly	missense_variant	Exon 20 of 20	ENST00000307790.8	NP_115580.2	Q9H1I8-1A0A024R1F9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC2	ENST00000307790.8 link	c.2177A>G	p.Glu726Gly	missense_variant	Exon 20 of 20	1	NM_032204.5	ENSP00000305502.3		Q9H1I8-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

251040

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000125

AC:

183

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000105

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

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

Jan 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2177A>G (p.E726G) alteration is located in exon 20 (coding exon 19) of the ASCC2 gene. This alteration results from a A to G substitution at nucleotide position 2177, causing the glutamic acid (E) at amino acid position 726 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

T;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.061

T;D;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.95

P;.;P

Vest4

0.23

MVP

0.33

MPC

0.87

ClinPred

0.15

GERP RS

5.9

Varity_R

0.16

gMVP

0.095

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