2-38309477-G-T

Variant names:

• chr2-38309477-G-T
• rs763899562
• NM_001135673.4:c.973C>A

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.973C>A​(p.Arg325Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,460,272 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATL2 NM_001135673.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• 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 (REVEL=0.083).

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.973C>A	p.Arg325Arg	synonymous	Exon 9 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001330463.2		c.973C>A	p.Arg325Arg	synonymous	Exon 9 of 14	NP_001317392.1
	ATL2	NM_001330462.1		c.958C>A	p.Arg320Arg	synonymous	Exon 9 of 14	NP_001317391.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL2	ENST00000378954.9	TSL:1 MANE Select	c.973C>A	p.Arg325Arg	synonymous	Exon 9 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*578C>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*578C>A		3_prime_UTR	Exon 8 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460272 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726502

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		3.6
Mutation Taster		=95/5	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: rs763899562; hg19: chr2-38536619;