7-6009468-C-G

Variant names:

• chr7-6009468-C-G
• rs529613640
• NM_006303.4:c.105C>G

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_006303.4(AIMP2):​c.105C>G​(p.Tyr35*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIMP2 NM_006303.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP2	NM_006303.4	MANE Select	c.105C>G	p.Tyr35*	stop_gained	Exon 1 of 4	NP_006294.2
	AIMP2	NM_001326607.2		c.105C>G	p.Tyr35*	stop_gained	Exon 1 of 3	NP_001313536.1
	AIMP2	NM_001326609.2		c.-216C>G		5_prime_UTR	Exon 1 of 5	NP_001313538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP2	ENST00000223029.8	TSL:1 MANE Select	c.105C>G	p.Tyr35*	stop_gained	Exon 1 of 4	ENSP00000223029.3
	AIMP2	ENST00000395236.2	TSL:2	c.105C>G	p.Tyr35*	stop_gained	Exon 1 of 3	ENSP00000378658.2
	AIMP2	ENST00000400479.6	TSL:5	c.-251+90C>G		intron	N/A	ENSP00000383327.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	35
DANN	Benign	0.97
Eigen	Benign	0.099
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.48	N
PhyloP100		1.1
Vest4		0.62
GERP RS		3.1
PromoterAI		0.019	Neutral
Mutation Taster		=8/192	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs529613640; hg19: chr7-6049099;