rs6760123

Variant names:

• chr2-38375369-C-T
• rs6760123
• NM_001135673.4:c.118+1774G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135673.4(ATL2):​c.118+1774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,984 control chromosomes in the GnomAD database, including 10,026 homozygotes. 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: 𝑓 0.36 (10026 hom., cov: 32)
• Consequence: ATL2 NM_001135673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL2	NM_001135673.4	MANE Select	c.118+1774G>A		intron	N/A	NP_001129145.1
	ATL2	NM_001330463.2		c.118+1774G>A		intron	N/A	NP_001317392.1
	ATL2	NM_001330462.1		c.103+2653G>A		intron	N/A	NP_001317391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL2	ENST00000378954.9	TSL:1 MANE Select	c.118+1774G>A		intron	N/A	ENSP00000368237.4
	ATL2	ENST00000405384.6	TSL:1	n.118+1774G>A		intron	N/A	ENSP00000383944.2
	ATL2	ENST00000419554.6	TSL:2	c.118+1774G>A		intron	N/A	ENSP00000415336.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54775 AN: 151864 Hom.: 10027 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54804 AN: 151984 Hom.: 10026 Cov.: 32 AF XY: 0.363 AC XY: 26991 AN XY: 74264

African (AFR) AF: 0.340 AC: 14107 AN: 41452

American (AMR) AF: 0.331 AC: 5061 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3470

East Asian (EAS) AF: 0.123 AC: 638 AN: 5176

South Asian (SAS) AF: 0.463 AC: 2234 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4222 AN: 10530

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26279 AN: 67956

Other (OTH) AF: 0.359 AC: 755 AN: 2104

Alfa AF: 0.390 Hom.: 6052

Bravo AF: 0.349

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.82
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

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: rs6760123; hg19: chr2-38602511;