chr21-46484793-C-A

Variant names:

• chr21-46484793-C-A
• rs747118563
• NM_015151.4:c.128C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015151.4(DIP2A):​c.128C>A​(p.Ala43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,528 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DIP2A NM_015151.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.128C>A	p.Ala43Glu	missense_variant	Exon 2 of 38	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.128C>A	p.Ala43Glu	missense_variant	Exon 2 of 38	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000485 AC: 1 AN: 206146 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 110232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000346

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432528 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000249

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: 0.00

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	0.30
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	.;.;.;.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.7	L;L;L;L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.014	D;D;D;D;D
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.73, 0.99, 0.60, 0.49	.;P;D;P;P
Vest4		0.82
MutPred		0.75		Gain of disorder (P = 0.0331);Gain of disorder (P = 0.0331);Gain of disorder (P = 0.0331);Gain of disorder (P = 0.0331);Gain of disorder (P = 0.0331);
MVP		0.31
MPC		0.37
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.40
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747118563; hg19: chr21-47904706;