rs2394522

Variant names:

• chr10-69152515-G-C
• rs2394522
• NM_004896.5:c.154-3297G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-69152515-G-C
• chr10-69152515-G-T

Variant summary

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

The NM_004896.5(VPS26A):​c.154-3297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,010 control chromosomes in the GnomAD database, including 2,777 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 0.18 (2777 hom., cov: 31)
• Consequence: VPS26A NM_004896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 1 publications found

Genes affected

VPS26A (HGNC:12711): (VPS26 retromer complex component A) This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004896.5. 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
	VPS26A	NM_004896.5	MANE Select	c.154-3297G>C		intron	N/A	NP_004887.2
	VPS26A	NM_001318944.2		c.133-3297G>C		intron	N/A	NP_001305873.1
	VPS26A	NM_001318945.2		c.103-3297G>C		intron	N/A	NP_001305874.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26A	ENST00000263559.11	TSL:1 MANE Select	c.154-3297G>C		intron	N/A	ENSP00000263559.6	O75436-1
	VPS26A	ENST00000949228.1		c.154-3297G>C		intron	N/A	ENSP00000619287.1
	VPS26A	ENST00000858435.1		c.154-3297G>C		intron	N/A	ENSP00000528494.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26972 AN: 151892 Hom.: 2771 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.178 AC: 26982 AN: 152010 Hom.: 2777 Cov.: 31 AF XY: 0.178 AC XY: 13253 AN XY: 74292

African (AFR) AF: 0.0998 AC: 4140 AN: 41486

American (AMR) AF: 0.130 AC: 1980 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.0346 AC: 179 AN: 5170

South Asian (SAS) AF: 0.132 AC: 635 AN: 4818

European-Finnish (FIN) AF: 0.328 AC: 3448 AN: 10520

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15487 AN: 67952

Other (OTH) AF: 0.147 AC: 309 AN: 2108

Alfa AF: 0.195 Hom.: 396

Bravo AF: 0.159

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.61
PhyloP100		-0.32
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: rs2394522; hg19: chr10-70912271;