rs6760123

Positions:

• chr2-38375369-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATL2	NM_001135673.4	c.118+1774G>A		intron_variant		ENST00000378954.9	NP_001129145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATL2	ENST00000378954.9	c.118+1774G>A		intron_variant		1	NM_001135673.4	ENSP00000368237	P1

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.359

Alfa AF: 0.390 Hom.: 5468

Bravo AF: 0.349

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs6760123; hg19: chr2-38602511;