21-46490692-G-T

Variant names:

• chr21-46490692-G-T
• rs781249841
• NM_015151.4:c.256G>T

Variant summary

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

The NM_015151.4(DIP2A):​c.256G>T​(p.Ala86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DIP2A NM_015151.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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]

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=0.030153185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.256G>T	p.Ala86Ser	missense_variant	Exon 3 of 38	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.256G>T	p.Ala86Ser	missense_variant	Exon 3 of 38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433626 Hom.: 0 Cov.: 32 AF XY: 0.00000282 AC XY: 2 AN XY: 710382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.8
DANN	Benign	0.79
DEOGEN2	Benign	0.014	.;.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.54	T;T;T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.030	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.40	N;N;N;N;N
REVEL	Benign	0.067
Sift	Benign	0.52	T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;B;B
Vest4		0.047
MutPred		0.23		Gain of phosphorylation at A86 (P = 0.0013);Gain of phosphorylation at A86 (P = 0.0013);Gain of phosphorylation at A86 (P = 0.0013);Gain of phosphorylation at A86 (P = 0.0013);Gain of phosphorylation at A86 (P = 0.0013);
MVP		0.18
MPC		0.25
ClinPred		0.053	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.024
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs781249841; hg19: chr21-47910605;