chr2-219221254-G-C

Variant names:

• chr2-219221254-G-C
• rs769517669
• NM_001077198.3:c.2194C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001077198.3(ATG9A):​c.2194C>G​(p.Arg732Gly) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R732C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077198.3. 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
	ATG9A	NM_001077198.3	MANE Select	c.2194C>G	p.Arg732Gly	missense	Exon 14 of 16	NP_001070666.1	Q7Z3C6-1
	ATG9A	NM_024085.5		c.2194C>G	p.Arg732Gly	missense	Exon 13 of 15	NP_076990.4
	ATG9A	NR_104255.2		n.2318C>G		non_coding_transcript_exon	Exon 14 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9A	ENST00000361242.9	TSL:2 MANE Select	c.2194C>G	p.Arg732Gly	missense	Exon 14 of 16	ENSP00000355173.4	Q7Z3C6-1
	ATG9A	ENST00000396761.6	TSL:1	c.2194C>G	p.Arg732Gly	missense	Exon 13 of 15	ENSP00000379983.2	Q7Z3C6-1
	ATG9A	ENST00000409033.7	TSL:1	n.*548C>G		non_coding_transcript_exon	Exon 14 of 16	ENSP00000386482.3	Q7Z3C6-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.24		Loss of stability (P = 0.0847)
MVP		0.63
MPC		0.38
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.29
gMVP		0.58
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs769517669; hg19: chr2-220085976;