Genetic Variant AIMP2:c.-22C>A (chr7-6009342-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006303.4(AIMP2):c.-22C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,611,438 control chromosomes in the GnomAD database, including 38,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.24 ( 4559 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33732 hom. )

Consequence

AIMP2
NM_006303.4 5_prime_UTR

Scores

Clinical Significance

Benign reviewed by expert panel B:1

Conservation

PhyloP100: -0.387

Variant links:

Genes affected

AIMP2 (HGNC:20609): (aminoacyl tRNA synthetase complex interacting multifunctional protein 2) The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]

AIMP2 links:

PMS2 (HGNC:9122): (PMS1 homolog 2, mismatch repair system component) The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]

PMS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 7-6009342-C-A is Benign according to our data. Variant chr7-6009342-C-A is described in ClinVar as [Benign]. Clinvar id is 91284.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-6009342-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP2	NM_006303.4 link	c.-22C>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000223029.8	NP_006294.2	Q13155-1A0A024QZY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP2	ENST00000223029 link	c.-22C>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_006303.4	ENSP00000223029.3		Q13155-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35864

AN:

151960

Hom.:

4553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.211

AC:

52714

AN:

250350

Hom.:

6004

AF XY:

0.212

AC XY:

28778

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.212

AC:

308709

AN:

1459360

Hom.:

33732

Cov.:

AF XY:

0.212

AC XY:

154060

AN XY:

725994

show subpopulations

Gnomad4 AFR exome

AF:

0.322

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.236

AC:

35873

AN:

152078

Hom.:

4559

Cov.:

AF XY:

0.237

AC XY:

17655

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.209

Hom.:

4379

Bravo

AF:

0.231

Asia WGS

AF:

0.194

AC:

674

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Lynch syndrome

Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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