2-38296034-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135673.4(ATL2):​c.1712C>G​(p.Thr571Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. T571I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATL2 NM_001135673.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18609136).

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>G	p.Thr571Ser	missense	Exon 13 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001308076.1		c.1658C>G	p.Thr553Ser	missense	Exon 13 of 13	NP_001295005.1	Q8NHH9-5
	ATL2	NM_001330458.2		c.1199C>G	p.Thr400Ser	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>G	p.Thr571Ser	missense	Exon 13 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>G		3_prime_UTR	Exon 12 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.087
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.14	N
REVEL	Uncertain	0.35
Sift	Benign	0.46	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.17		Gain of loop (P = 0.024)
MVP		0.78
MPC		0.12
ClinPred		0.64	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.40
Mutation Taster		=62/38	polymorphism

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;