2-38296034-G-A

Variant names:

• chr2-38296034-G-A
• rs1359820555
• NM_001135673.4:c.1712C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135673.4(ATL2):​c.1712C>T​(p.Thr571Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATL2 NM_001135673.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

Genes affected

ATL2 (HGNC:24047): (atlastin GTPase 2) Enables identical protein binding activity. Involved in Golgi organization; endoplasmic reticulum tubular network membrane organization; and protein homooligomerization. Located in endoplasmic reticulum tubular network membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATL2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35419703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135673.4. 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
	ATL2	NM_001135673.4	MANE Select	c.1712C>T	p.Thr571Ile	missense	Exon 13 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001308076.1		c.1658C>T	p.Thr553Ile	missense	Exon 13 of 13	NP_001295005.1	Q8NHH9-5
	ATL2	NM_001330458.2		c.1199C>T	p.Thr400Ile	missense	Exon 12 of 12	NP_001317387.1	Q8NHH9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL2	ENST00000378954.9	TSL:1 MANE Select	c.1712C>T	p.Thr571Ile	missense	Exon 13 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>T		3_prime_UTR	Exon 12 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399446 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690218

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078800

Other (OTH) AF: 0.00 AC: 0 AN: 58122

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.23	T
Polyphen		0.31	B
Vest4		0.46
MutPred		0.34		Loss of loop (P = 0.0235)
MVP		0.89
MPC		0.19
ClinPred		0.90	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.58
Mutation Taster		=46/54	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: rs1359820555; hg19: chr2-38523176;