Genetic Variant NM_032204.5:c.2020A>C (chr22-29792435-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032204.5(ASCC2):c.2020A>C(p.Lys674Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00019 in 1,613,890 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

ASCC2
NM_032204.5 missense, splice_region

Scores

Splicing: ADA: 0.004736

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16792119).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ASCC2	NM_032204.5	MANE Select	c.2020A>C	p.Lys674Gln	missense splice_region	Exon 18 of 20	NP_115580.2
ASCC2	NM_001369920.1		c.2020A>C	p.Lys674Gln	missense	Exon 18 of 20	NP_001356849.1
ASCC2	NM_001369925.1		c.1861A>C	p.Lys621Gln	missense	Exon 17 of 19	NP_001356854.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASCC2	ENST00000307790.8	TSL:1 MANE Select	c.2020A>C	p.Lys674Gln	missense splice_region	Exon 18 of 20	ENSP00000305502.3	Q9H1I8-1
ASCC2	ENST00000865563.1		c.2020A>C	p.Lys674Gln	missense	Exon 18 of 20	ENSP00000535622.1
ASCC2	ENST00000865575.1		c.2020A>C	p.Lys674Gln	missense	Exon 19 of 21	ENSP00000535634.1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000207

AC:

AN:

251420

AF XY:

0.000213

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000191

AC:

279

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

137

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.000268

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000181

AC:

201

AN:

1111818

Other (OTH)

AF:

0.000547

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41568

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68010

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.018

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.0070

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.70

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

PhyloP100

4.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

REVEL

Benign

0.095

Sift

Uncertain

0.018

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.64

MVP

0.28

MPC

0.36

ClinPred

0.093

GERP RS

5.0

Varity_R

0.26

gMVP

0.12

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0047

dbscSNV1_RF

Benign

0.026

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over