rs2955384

Variant names:

• chr17-18036259-G-A
• rs2955384
• NM_145691.4:c.133+2622C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-18036259-G-A
• chr17-18036259-G-C
• chr17-18036259-G-T

Variant summary

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

The NM_145691.4(ATPAF2):​c.133+2622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,794 control chromosomes in the GnomAD database, including 13,412 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 0.40 (13412 hom., cov: 31)
• Consequence: ATPAF2 NM_145691.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 13 publications found

Genes affected

ATPAF2 (HGNC:18802): (ATP synthase mitochondrial F1 complex assembly factor 2) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

ATPAF2 Gene-Disease associations (from GenCC):

• mitochondrial proton-transporting ATP synthase complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex V (ATP synthase) deficiency, nuclear type 1

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPAF2	NM_145691.4	c.133+2622C>T		intron_variant	Intron 1 of 7	ENST00000474627.8	NP_663729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPAF2	ENST00000474627.8	c.133+2622C>T		intron_variant	Intron 1 of 7	1	NM_145691.4	ENSP00000417190.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60988 AN: 151676 Hom.: 13405 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.402 AC: 61029 AN: 151794 Hom.: 13412 Cov.: 31 AF XY: 0.415 AC XY: 30796 AN XY: 74172

African (AFR) AF: 0.406 AC: 16804 AN: 41352

American (AMR) AF: 0.495 AC: 7555 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.869 AC: 4465 AN: 5140

South Asian (SAS) AF: 0.718 AC: 3444 AN: 4796

European-Finnish (FIN) AF: 0.396 AC: 4176 AN: 10540

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21810 AN: 67924

Other (OTH) AF: 0.405 AC: 853 AN: 2106

Alfa AF: 0.380 Hom.: 2418

Bravo AF: 0.409

Asia WGS AF: 0.705 AC: 2448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		0.077
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: rs2955384; hg19: chr17-17939573;