chr21-37237438-A-T

Variant names:

• chr21-37237438-A-T
• rs9305614
• NM_006052.2:c.351+1022T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006052.2(VPS26C):​c.351+1022T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: VPS26C NM_006052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 19 publications found

Genes affected

VPS26C (HGNC:3044): (VPS26 endosomal protein sorting factor C) The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and cognitive disability. The DSCR3 (Down syndrome critical region gene 3) gene is found in this region and is predictated to contain eight exons. DSCR3 is expressed in most tissues examined. [provided by RefSeq, Jul 2008]

ENSG00000242553 (HGNC:):

DSCR9 (HGNC:16301): (Down syndrome critical region 9)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006052.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26C	NM_006052.2	MANE Select	c.351+1022T>A		intron	N/A	NP_006043.1
	VPS26C	NM_001331022.1		c.351+1022T>A		intron	N/A	NP_001317951.1
	VPS26C	NM_001331021.1		c.207+1022T>A		intron	N/A	NP_001317950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26C	ENST00000309117.11	TSL:1 MANE Select	c.351+1022T>A		intron	N/A	ENSP00000311399.6
	VPS26C	ENST00000399000.7	TSL:1	n.976+1022T>A		intron	N/A
	VPS26C	ENST00000488368.5	TSL:1	n.442+1022T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		0.14

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: rs9305614; hg19: chr21-38609739;