Genetic Variant NM_033510.3:c.112C>G (chr15-40358433-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033510.3(DISP2):c.112C>G(p.Pro38Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,318,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P38R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

DISP2
NM_033510.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Publications

0 publications found

Variant links:

Genes affected

DISP2 (HGNC:19712): (dispatched RND transporter family member 2) This gene is one of two human homologs of a segment-polarity gene known as dispatched identified in Drosophila. The product of this gene may be required for normal Hedgehog (Hh) signaling during embryonic pattern formation. [provided by RefSeq, Jan 2017]

DISP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.07024887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033510.3. 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
	DISP2	NM_033510.3	MANE Select	c.112C>G	p.Pro38Ala	missense	Exon 1 of 8	NP_277045.1	A7MBM2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISP2	ENST00000267889.5	TSL:1 MANE Select	c.112C>G	p.Pro38Ala	missense	Exon 1 of 8	ENSP00000267889.3	A7MBM2
DISP2	ENST00000949525.1		c.112C>G	p.Pro38Ala	missense	Exon 1 of 8	ENSP00000619584.1
DISP2	ENST00000949524.1		c.112C>G	p.Pro38Ala	missense	Exon 1 of 8	ENSP00000619583.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000171

AC:

AN:

1166602

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

563342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23574

American (AMR)

AF:

0.00

AC:

AN:

9428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16026

East Asian (EAS)

AF:

0.00

AC:

AN:

26970

South Asian (SAS)

AF:

0.00

AC:

AN:

45430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4694

European-Non Finnish (NFE)

AF:

0.00000207

AC:

AN:

965970

Other (OTH)

AF:

0.00

AC:

AN:

46920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.0000263

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.54

M_CAP

Benign

0.029

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.035

Sift

Benign

0.26

Sift4G

Benign

0.47

Polyphen

0.0020

Vest4

0.079

MutPred

0.15

Loss of solvent accessibility (P = 0.0606)

MVP

0.12

MPC

0.37

ClinPred

0.21

GERP RS

3.9

PromoterAI

0.016

Neutral

(source)

Varity_R

0.086

gMVP

0.098

Mutation Taster

=90/10

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over