chr21-46498687-T-C

Position:

• chr21-46498687-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015151.4(DIP2A):​c.509T>C​(p.Val170Ala) 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. 15/21 in silico tools predict 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: DIP2A NM_015151.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.106

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050119728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.509T>C	p.Val170Ala	missense_variant	5/38	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.509T>C	p.Val170Ala	missense_variant	5/38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2024

The c.509T>C (p.V170A) alteration is located in exon 5 (coding exon 5) of the DIP2A gene. This alteration results from a T to C substitution at nucleotide position 509, causing the valine (V) at amino acid position 170 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.70
DEOGEN2	Benign	0.013	.;.;.;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.55	T;T;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.050	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.61	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.56	N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0, 0.0050, 0.0040	.;B;B;B;B
Vest4		0.10
MutPred		0.27		Loss of stability (P = 0.001);Loss of stability (P = 0.001);Loss of stability (P = 0.001);Loss of stability (P = 0.001);Loss of stability (P = 0.001);
MVP		0.21
MPC		0.31
ClinPred		0.054	T
GERP RS		-1.0
Varity_R		0.018
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47918600;