2-38300305-T-A

Variant names:

• chr2-38300305-T-A
• rs77626845
• NM_001135673.4:c.1095A>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001135673.4(ATL2):​c.1095A>T​(p.Gly365Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,609,476 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (219 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (215 hom.)
• Consequence: ATL2 NM_001135673.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-38300305-T-A is Benign according to our data. Variant chr2-38300305-T-A is described in ClinVar as Benign. ClinVar VariationId is 791852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATL2	NM_001135673.4	MANE Select	c.1095A>T	p.Gly365Gly	synonymous	Exon 10 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001330463.2		c.1095A>T	p.Gly365Gly	synonymous	Exon 10 of 14	NP_001317392.1
	ATL2	NM_001330462.1		c.1080A>T	p.Gly360Gly	synonymous	Exon 10 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.1095A>T	p.Gly365Gly	synonymous	Exon 10 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*700A>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*700A>T		3_prime_UTR	Exon 9 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4543 AN: 152114 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00795 AC: 1998 AN: 251188 AF XY: 0.00597

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00561

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00305 AC: 4445 AN: 1457244 Hom.: 215 Cov.: 30 AF XY: 0.00259 AC XY: 1877 AN XY: 725244

African (AFR) AF: 0.106 AC: 3542 AN: 33306

American (AMR) AF: 0.00669 AC: 299 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00469 AC: 27 AN: 5752

European-Non Finnish (NFE) AF: 0.000136 AC: 151 AN: 1108170

Other (OTH) AF: 0.00664 AC: 400 AN: 60242

GnomAD4 genome AF: 0.0300 AC: 4560 AN: 152232 Hom.: 219 Cov.: 32 AF XY: 0.0296 AC XY: 2204 AN XY: 74458

African (AFR) AF: 0.103 AC: 4284 AN: 41514

American (AMR) AF: 0.0131 AC: 200 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68018

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.00327 Hom.: 6

Bravo AF: 0.0340

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs77626845; hg19: chr2-38527447;