2-219221200-C-T

Variant names:

• chr2-219221200-C-T
• rs200858282
• NM_001077198.3:c.2248G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077198.3(ATG9A):​c.2248G>A​(p.Ala750Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000764 in 1,439,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022197515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9A	NM_001077198.3	c.2248G>A	p.Ala750Thr	missense_variant	Exon 14 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.2248G>A	p.Ala750Thr	missense_variant	Exon 13 of 15		NP_076990.4
ATG9A	NR_104255.2	n.2372G>A		non_coding_transcript_exon_variant	Exon 14 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9A	ENST00000361242.9	c.2248G>A	p.Ala750Thr	missense_variant	Exon 14 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.493G>A		non_coding_transcript_exon_variant	Exon 4 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000179 AC: 4 AN: 223514 Hom.: 0 AF XY: 0.0000246 AC XY: 3 AN XY: 121716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000652

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000764 AC: 11 AN: 1439618 Hom.: 0 Cov.: 35 AF XY: 0.0000112 AC XY: 8 AN XY: 714826

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.0000486

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: 0.00000726

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.5
DANN	Benign	0.85
DEOGEN2	Benign	0.037	T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.54	.;.;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.16	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.91	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.044
MutPred		0.11		Gain of phosphorylation at A750 (P = 0.0149);Gain of phosphorylation at A750 (P = 0.0149);Gain of phosphorylation at A750 (P = 0.0149);.;
MVP		0.40
MPC		0.21
ClinPred		0.026	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.029
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs200858282; hg19: chr2-220085922;