Genetic Variant DISP2:p.Pro18Ser (chr15-40358373-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_033510.3(DISP2):c.52C>T(p.Pro18Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DISP2
NM_033510.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.234

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:

ENSG00000289148 (HGNC:):

ENSG00000289148 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0390698).

BP6

Variant 15-40358373-C-T is Benign according to our data. Variant chr15-40358373-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3840214.Status of the report is criteria_provided_single_submitter, 1 stars.

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.52C>T	p.Pro18Ser	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.52C>T	p.Pro18Ser	missense	Exon 1 of 8	ENSP00000267889.3	A7MBM2
DISP2	ENST00000949525.1		c.52C>T	p.Pro18Ser	missense	Exon 1 of 8	ENSP00000619584.1
DISP2	ENST00000949524.1		c.52C>T	p.Pro18Ser	missense	Exon 1 of 8	ENSP00000619583.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1222100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

597844

African (AFR)

AF:

0.00

AC:

AN:

24862

American (AMR)

AF:

0.00

AC:

AN:

16346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19110

East Asian (EAS)

AF:

0.00

AC:

AN:

27540

South Asian (SAS)

AF:

0.00

AC:

AN:

55666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4320

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

995456

Other (OTH)

AF:

0.00

AC:

AN:

49420

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.062

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.1

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.14

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.35

M_CAP

Benign

0.021

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

PhyloP100

0.23

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.24

REVEL

Benign

0.017

Sift

Benign

0.89

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.078

MutPred

0.27

Gain of phosphorylation at P18 (P = 4e-04)

MVP

0.030

MPC

0.38

ClinPred

0.071

GERP RS

0.26

PromoterAI

-0.045

Neutral

(source)

Varity_R

0.021

gMVP

0.067

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over