17-30926896-A-C

Variant names:

• chr17-30926896-A-C
• NM_018404.3:c.295A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018404.3(ADAP2):​c.295A>C​(p.Ile99Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAP2 NM_018404.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.639
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09223503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018404.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP2	NM_018404.3	MANE Select	c.295A>C	p.Ile99Leu	missense	Exon 3 of 11	NP_060874.1	Q9NPF8-1
	ADAP2	NM_001346712.2		c.313A>C	p.Ile105Leu	missense	Exon 3 of 11	NP_001333641.1	Q2V6Q1
	ADAP2	NM_001346714.2		c.295A>C	p.Ile99Leu	missense	Exon 3 of 11	NP_001333643.1	Q9NPF8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP2	ENST00000330889.8	TSL:1 MANE Select	c.295A>C	p.Ile99Leu	missense	Exon 3 of 11	ENSP00000329468.3	Q9NPF8-1
	ADAP2	ENST00000580525.6	TSL:1	c.313A>C	p.Ile105Leu	missense	Exon 3 of 11	ENSP00000464121.1	Q2V6Q1
	ADAP2	ENST00000890570.1		c.358A>C	p.Ile120Leu	missense	Exon 4 of 12	ENSP00000560629.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.0
DANN	Benign	0.72
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.64
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.043
Sift	Benign	0.097	T
Sift4G	Uncertain	0.055	T
Polyphen		0.018	B
Vest4		0.29
MutPred		0.50		Loss of catalytic residue at Q107 (P = 0.1037)
MVP		0.10
MPC		0.53
ClinPred		0.072	T
GERP RS		-6.7
Varity_R		0.073
gMVP		0.39

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

Other links and lift over

hg19: chr17-29253914;