Variant 7-6009437-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_006303.4(AIMP2):c.74A>G(p.Tyr25Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AIMP2
NM_006303.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.33

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.865

PP5

Variant 7-6009437-A-G is Pathogenic according to our data. Variant chr7-6009437-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 982311.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIMP2	NM_006303.4 linkuse as main transcript	c.74A>G	p.Tyr25Cys	missense_variant	1/4	ENST00000223029.8	NP_006294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIMP2	ENST00000223029.8 linkuse as main transcript	c.74A>G	p.Tyr25Cys	missense_variant	1/4	1	NM_006303.4	ENSP00000223029	P1	Q13155-1
AIMP2	ENST00000395236.2 linkuse as main transcript	c.74A>G	p.Tyr25Cys	missense_variant	1/3	2		ENSP00000378658		Q13155-2
AIMP2	ENST00000400479.6 linkuse as main transcript	c.-251+59A>G		intron_variant		5		ENSP00000383327
AIMP2	ENST00000415999.1 linkuse as main transcript	c.74A>G	p.Tyr25Cys	missense_variant, NMD_transcript_variant	1/3	3		ENSP00000392519

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725726

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leukodystrophy, hypomyelinating, 17

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences

Analysis of the exome sequencing data showed a novel homozygous sequence variant in AIMP2 gene. This variant is predicted as Disease Causing by MutationTaster. This variant is not found in ExAC and 1000G databases. Sanger sequencing confirmed the variation in the proband and similarly affected female sibling. Parents are heterozygous for the same variation. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.95

MutPred

0.58

Loss of phosphorylation at Y25 (P = 0.0243);Loss of phosphorylation at Y25 (P = 0.0243);

MVP

0.75

MPC

0.26

ClinPred

1.0

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.95

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over