17-30926917-C-G

Variant names:

• chr17-30926917-C-G
• rs773464152
• NM_018404.3:c.316C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018404.3(ADAP2):​c.316C>G​(p.Leu106Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ADAP2 NM_018404.3 missense, splice_region
• Scores: Splicing: ADA: 0.001109
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.09
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.066449255).

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.316C>G	p.Leu106Val	missense splice_region	Exon 3 of 11	NP_060874.1	Q9NPF8-1
	ADAP2	NM_001346712.2		c.334C>G	p.Leu112Val	missense splice_region	Exon 3 of 11	NP_001333641.1	Q2V6Q1
	ADAP2	NM_001346714.2		c.316C>G	p.Leu106Val	missense splice_region	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.316C>G	p.Leu106Val	missense splice_region	Exon 3 of 11	ENSP00000329468.3	Q9NPF8-1
	ADAP2	ENST00000580525.6	TSL:1	c.334C>G	p.Leu112Val	missense splice_region	Exon 3 of 11	ENSP00000464121.1	Q2V6Q1
	ADAP2	ENST00000890570.1		c.379C>G	p.Leu127Val	missense splice_region	Exon 4 of 12	ENSP00000560629.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251288 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460254 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726576

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.000112 AC: 5 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110560

Other (OTH) AF: 0.000133 AC: 8 AN: 60340

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152198 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.000524 AC: 8 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.0000330 AC: 4

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	0.072
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.9
DANN	Benign	0.89
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-2.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.032
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Polyphen		0.0070	B
Vest4		0.18
MutPred		0.49		Loss of catalytic residue at L112 (P = 0.0299)
MVP		0.28
MPC		0.83
ClinPred		0.037	T
GERP RS		-0.75
Varity_R		0.058
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.11		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

dbSNP: rs773464152; hg19: chr17-29253935;