2-38296034-G-T

Variant names:

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

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>A​(p.Thr571Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000058 in 1,551,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2829189).

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>A	p.Thr571Asn	missense	Exon 13 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001308076.1		c.1658C>A	p.Thr553Asn	missense	Exon 13 of 13	NP_001295005.1	Q8NHH9-5
	ATL2	NM_001330458.2		c.1199C>A	p.Thr400Asn	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>A	p.Thr571Asn	missense	Exon 13 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*1317C>A		3_prime_UTR	Exon 12 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000634 AC: 1 AN: 157834 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000572 AC: 8 AN: 1399446 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 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: 0.00000742 AC: 8 AN: 1078800

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.073
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.044	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.27	N
REVEL	Uncertain	0.32
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.49
MutPred		0.18		Gain of loop (P = 0.024)
MVP		0.73
MPC		0.15
ClinPred		0.46	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.59
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: rs1359820555; hg19: chr2-38523176;