chr2-38298499-A-G

Variant names:

• chr2-38298499-A-G
• NM_001135673.4:c.1277T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135673.4(ATL2):​c.1277T>C​(p.Ile426Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATL2 NM_001135673.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.13
• 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=0.30361864).

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.1277T>C	p.Ile426Thr	missense	Exon 12 of 13	NP_001129145.1	Q8NHH9-1
	ATL2	NM_001330463.2		c.1277T>C	p.Ile426Thr	missense	Exon 12 of 14	NP_001317392.1
	ATL2	NM_001330462.1		c.1262T>C	p.Ile421Thr	missense	Exon 12 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.1277T>C	p.Ile426Thr	missense	Exon 12 of 13	ENSP00000368237.4	Q8NHH9-1
	ATL2	ENST00000405384.6	TSL:1	n.*882T>C		non_coding_transcript_exon	Exon 11 of 12	ENSP00000383944.2	F8WD17
	ATL2	ENST00000405384.6	TSL:1	n.*882T>C		3_prime_UTR	Exon 11 of 12	ENSP00000383944.2	F8WD17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	0.043
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.1
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.48	P
Vest4		0.52
MutPred		0.55		Loss of stability (P = 0.0047)
MVP		0.24
MPC		0.22
ClinPred		0.92	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.50
Mutation Taster		=44/56	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

hg19: chr2-38525641;