Genetic Variant TULP2:p.Ala18Thr (chr19-48897377-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003323.3(TULP2):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,196 control chromosomes in the GnomAD database, including 16,713 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3115 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13598 hom. )

Consequence

TULP2
NM_003323.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.128

Publications

33 publications found

Variant links:

Genes affected

TULP2 (HGNC:12424): (TUB like protein 2) TULP2 is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates, and invertebrates. The TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. [provided by RefSeq, Jul 2008]

TULP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TULP2	NM_003323.3 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 13	ENST00000221399.8	NP_003314.2	O00295

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP2	ENST00000221399.8 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 13	1	NM_003323.3	ENSP00000221399.3		O00295

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27558

AN:

151972

Hom.:

3108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0711

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.190

GnomAD2 exomes

AF:

0.148

AC:

37035

AN:

249958

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0696

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.129

AC:

188684

AN:

1461106

Hom.:

13598

Cov.:

AF XY:

0.130

AC XY:

94677

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.330

AC:

11056

AN:

33462

American (AMR)

AF:

0.180

AC:

8010

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4108

AN:

26114

East Asian (EAS)

AF:

0.0687

AC:

2728

AN:

39688

South Asian (SAS)

AF:

0.184

AC:

15821

AN:

86132

European-Finnish (FIN)

AF:

0.135

AC:

7228

AN:

53382

Middle Eastern (MID)

AF:

0.133

AC:

770

AN:

5768

European-Non Finnish (NFE)

AF:

0.117

AC:

130522

AN:

1111614

Other (OTH)

AF:

0.140

AC:

8441

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

8521

17042

25564

34085

42606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4928

9856

14784

19712

24640

<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

AF:

0.181

AC:

27592

AN:

152090

Hom.:

3115

Cov.:

AF XY:

0.181

AC XY:

13486

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.319

AC:

13210

AN:

41444

American (AMR)

AF:

0.178

AC:

2724

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

540

AN:

3464

East Asian (EAS)

AF:

0.0707

AC:

366

AN:

5178

South Asian (SAS)

AF:

0.192

AC:

924

AN:

4822

European-Finnish (FIN)

AF:

0.126

AC:

1337

AN:

10606

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7979

AN:

67986

Other (OTH)

AF:

0.188

AC:

395

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1085

2170

3256

4341

5426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

7676

Bravo

AF:

0.189

TwinsUK

AF:

0.114

AC:

423

ALSPAC

AF:

0.118

AC:

453

ESP6500AA

AF:

0.315

AC:

1386

ESP6500EA

AF:

0.120

AC:

1029

ExAC

AF:

0.150

AC:

18262

Asia WGS

AF:

0.135

AC:

471

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.1

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0054

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.40

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

-0.13

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.039

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.46

T;.;.

Polyphen

0.062

B;.;.

Vest4

0.015

MPC

1.0

ClinPred

0.00070

GERP RS

-0.41

PromoterAI

0.090

Neutral

(source)

Varity_R

0.036

gMVP

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over