2-219222102-A-G

Variant names:

• chr2-219222102-A-G
• NM_001077198.3:c.2093T>C

Variant summary

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

The NM_001077198.3(ATG9A):​c.2093T>C​(p.Leu698Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.21

Genes affected

ATG9A (HGNC:22408): (autophagy related 9A) Acts upstream of or within autophagosome assembly. Located in endosome; phagophore assembly site; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284820 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9A	NM_001077198.3	c.2093T>C	p.Leu698Pro	missense_variant	Exon 13 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.2093T>C	p.Leu698Pro	missense_variant	Exon 12 of 15		NP_076990.4
ATG9A	NR_104255.2	n.2217T>C		non_coding_transcript_exon_variant	Exon 13 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9A	ENST00000361242.9	c.2093T>C	p.Leu698Pro	missense_variant	Exon 13 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.338T>C		non_coding_transcript_exon_variant	Exon 3 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727208

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T;T;T;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;.;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.51	N;N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.21	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.95
MutPred		0.37		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);.;
MVP		0.59
MPC		1.0
ClinPred		0.82	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.56

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: chr2-220086824;