Genetic Variant NM_018404.3:c.641A>C (chr17-30945037-A-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018404.3(ADAP2):c.641A>C(p.Tyr214Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y214C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADAP2
NM_018404.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.38

Publications

0 publications found

Variant links:

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]

ADAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP2	NM_018404.3	MANE Select	c.641A>C	p.Tyr214Ser	missense	Exon 6 of 11	NP_060874.1	Q9NPF8-1
ADAP2	NM_001346712.2		c.659A>C	p.Tyr220Ser	missense	Exon 6 of 11	NP_001333641.1	Q2V6Q1
ADAP2	NM_001346714.2		c.641A>C	p.Tyr214Ser	missense	Exon 6 of 11	NP_001333643.1	Q9NPF8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP2	ENST00000330889.8	TSL:1 MANE Select	c.641A>C	p.Tyr214Ser	missense	Exon 6 of 11	ENSP00000329468.3	Q9NPF8-1
ADAP2	ENST00000580525.6	TSL:1	c.659A>C	p.Tyr220Ser	missense	Exon 6 of 11	ENSP00000464121.1	Q2V6Q1
ADAP2	ENST00000890570.1		c.704A>C	p.Tyr235Ser	missense	Exon 7 of 12	ENSP00000560629.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111954

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.57

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.2

PhyloP100

7.4

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-8.8

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Benign

0.092

Polyphen

1.0

Vest4

0.85

MutPred

0.60

Gain of disorder (P = 0.0072)

MVP

0.93

MPC

1.4

ClinPred

1.0

GERP RS

5.2

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.87

gMVP

0.79

Mutation Taster

=40/60

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over