dbSNP rs767064905: AIMP2:p.Thr195Thr (chr7-6023313-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_006303.4(AIMP2):c.585G>A(p.Thr195Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,598,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AIMP2
NM_006303.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.39

Publications

0 publications found

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:

EIF2AK1 (HGNC:24921): (eukaryotic translation initiation factor 2 alpha kinase 1) The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

EIF2AK1 Gene-Disease associations (from GenCC):

leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

EIF2AK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-6023313-G-A is Benign according to our data. Variant chr7-6023313-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3029218.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.39 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006303.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AIMP2	NM_006303.4	MANE Select	c.585G>A	p.Thr195Thr	synonymous	Exon 4 of 4	NP_006294.2
EIF2AK1	NM_014413.4	MANE Select	c.*1360C>T		3_prime_UTR	Exon 15 of 15	NP_055228.2
AIMP2	NM_001362785.2		c.498G>A	p.Thr166Thr	synonymous	Exon 5 of 5	NP_001349714.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIMP2	ENST00000223029.8	TSL:1 MANE Select	c.585G>A	p.Thr195Thr	synonymous	Exon 4 of 4	ENSP00000223029.3	Q13155-1
EIF2AK1	ENST00000199389.11	TSL:1 MANE Select	c.*1360C>T		3_prime_UTR	Exon 15 of 15	ENSP00000199389.6	Q9BQI3-1
AIMP2	ENST00000395236.2	TSL:2	c.378G>A	p.Thr126Thr	synonymous	Exon 3 of 3	ENSP00000378658.2	Q13155-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

239156

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1446686

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718926

show subpopulations

African (AFR)

AF:

0.0000613

AC:

AN:

32644

American (AMR)

AF:

0.0000237

AC:

AN:

42250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25310

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39592

South Asian (SAS)

AF:

0.0000950

AC:

AN:

84254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1105938

Other (OTH)

AF:

0.0000168

AC:

AN:

59682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000318

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

AIMP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.84

(source)

DANN

Benign

0.85

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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