rs139876370

Variant names:

• chr17-30934221-A-C
• rs139876370
• NM_018404.3:c.434A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-30934221-A-C
• chr17-30934221-A-G

Variant summary

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

The NM_018404.3(ADAP2):​c.434A>C​(p.Asp145Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D145G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAP2 NM_018404.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

Genes affected

ADAP2 (HGNC:16487): (ArfGAP with dual PH domains 2) The protein encoded by this gene binds beta-tubulin and increases the stability of microtubules. The encoded protein can also translocate to the cell membrane and bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). In addition, this protein is a GTPase-activating protein for ADP ribosylation factor 6 and may be able to block the entry of some RNA viruses. [provided by RefSeq, Oct 2016]

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=0.41680947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAP2	NM_018404.3	c.434A>C	p.Asp145Ala	missense_variant	Exon 5 of 11	ENST00000330889.8	NP_060874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAP2	ENST00000330889.8	c.434A>C	p.Asp145Ala	missense_variant	Exon 5 of 11	1	NM_018404.3	ENSP00000329468.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Uncertain	0.54	D;.;D;.
Eigen	Benign	0.023
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.5	D;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.033	D;.;.;.
Sift4G	Benign	0.092	T;D;T;T
Polyphen		0.034	B;.;B;.
Vest4		0.38
MutPred		0.46		.;.;Loss of solvent accessibility (P = 0.0769);.;
MVP		0.78
MPC		0.54
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.45
gMVP		0.60

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: rs139876370; hg19: chr17-29261239;