chr21-46490714-G-A

Variant names:

• chr21-46490714-G-A
• rs747941265
• NM_015151.4:c.278G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015151.4(DIP2A):​c.278G>A​(p.Arg93Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000493 in 1,420,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: DIP2A NM_015151.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.03

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4078466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.278G>A	p.Arg93Gln	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.278G>A	p.Arg93Gln	missense_variant	Exon 3 of 38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000493 AC: 7 AN: 1420238 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 2 AN XY: 702666

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: 0.00000550

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	.;.;.;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		0.99, 0.81, 0.99, 0.96	.;D;P;D;D
Vest4		0.53
MutPred		0.39		Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);Loss of MoRF binding (P = 0.0476);
MVP		0.56
MPC		0.77
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs747941265; hg19: chr21-47910627;