6-143450589-T-C

Position:

• chr6-143450589-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000237283.9(ADAT2):​c.70A>G​(p.Lys24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K24N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADAT2 ENST00000237283.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

Genes affected

ADAT2 (HGNC:21172): (adenosine deaminase tRNA specific 2) Predicted to enable tRNA-specific adenosine-34 deaminase activity. Predicted to be involved in tRNA wobble adenosine to inosine editing. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ADAT2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18463778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAT2	NM_182503.3	c.70A>G	p.Lys24Glu	missense_variant	1/6	ENST00000237283.9	NP_872309.2
ADAT2	XM_011535439.3	c.70A>G	p.Lys24Glu	missense_variant	1/9		XP_011533741.1
ADAT2	XM_011535443.2	c.70A>G	p.Lys24Glu	missense_variant	1/6		XP_011533745.1
ADAT2	XM_047418189.1	c.-114A>G		5_prime_UTR_variant	1/7		XP_047274145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAT2	ENST00000237283.9	c.70A>G	p.Lys24Glu	missense_variant	1/6	1	NM_182503.3	ENSP00000237283.8
ADAT2	ENST00000367593.1	n.85A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.70A>G (p.K24E) alteration is located in exon 1 (coding exon 1) of the ADAT2 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the lysine (K) at amino acid position 24 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.79	N
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.077
Sift	Benign	0.50	T
Sift4G	Benign	0.89	T
Polyphen		0.0080	B
Vest4		0.44
MutPred		0.47		Loss of methylation at K24 (P = 0.0032);
MVP		0.59
MPC		0.53
ClinPred		0.21	T
GERP RS		3.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.24
gMVP		0.85

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.

Other links and lift over

hg19: chr6-143771726;