rs535903034

Variant names:

• chr21-46490625-G-T
• rs535903034
• NM_015151.4:c.189G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-46490625-G-T
• chr21-46490625-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015151.4(DIP2A):​c.189G>T​(p.Glu63Asp) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DIP2A NM_015151.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.493
• Publications: 1 publications found

Genes affected

DIP2A (HGNC:17217): (disco interacting protein 2 homolog A) The protein encoded by this gene may be involved in axon patterning in the central nervous system. This gene is not highly expressed. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

DIP2A Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09392339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015151.4. 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
	DIP2A	NM_015151.4	MANE Select	c.189G>T	p.Glu63Asp	missense	Exon 3 of 38	NP_055966.2
	DIP2A	NM_001410751.1		c.189G>T	p.Glu63Asp	missense	Exon 3 of 39	NP_001397680.1	A0A494C143
	DIP2A	NM_001353942.2		c.189G>T	p.Glu63Asp	missense	Exon 3 of 38	NP_001340871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2A	ENST00000417564.3	TSL:1 MANE Select	c.189G>T	p.Glu63Asp	missense	Exon 3 of 38	ENSP00000392066.2	Q14689-1
	DIP2A	ENST00000457905.7	TSL:1	c.189G>T	p.Glu63Asp	missense	Exon 3 of 22	ENSP00000393434.3	Q14689-4
	DIP2A	ENST00000466639.5	TSL:1	c.189G>T	p.Glu63Asp	missense	Exon 3 of 20	ENSP00000430249.1	Q14689-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 194554 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426122 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 705988

African (AFR) AF: 0.00 AC: 0 AN: 32724

American (AMR) AF: 0.00 AC: 0 AN: 38820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 37854

South Asian (SAS) AF: 0.00 AC: 0 AN: 81212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094014

Other (OTH) AF: 0.00 AC: 0 AN: 59138

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000833 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	DIP2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.49
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.041
Sift	Benign	0.19	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.30		Loss of helix (P = 0.0444)
MVP		0.33
MPC		0.33
ClinPred		0.14	T
GERP RS		4.3
Varity_R		0.046
gMVP		0.10
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs535903034; hg19: chr21-47910538;