15-40363779-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033510.3(DISP2):​c.274C>T​(p.His92Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

DISP2
NM_033510.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07754001).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DISP2NM_033510.3 linkc.274C>T p.His92Tyr missense_variant Exon 2 of 8 ENST00000267889.5 NP_277045.1
LOC124903472XR_007064597.1 linkn.2418-642G>A intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DISP2ENST00000267889.5 linkc.274C>T p.His92Tyr missense_variant Exon 2 of 8 1 NM_033510.3 ENSP00000267889.3 A7MBM2

Frequencies

GnomAD3 genomes
AF:
0.000762
AC:
116
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
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:
0.00129
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000515
AC:
129
AN:
250576
Hom.:
0
AF XY:
0.000539
AC XY:
73
AN XY:
135456
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000435
Gnomad ASJ exome
AF:
0.0000998
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000927
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.00105
AC:
1531
AN:
1461200
Hom.:
0
Cov.:
35
AF XY:
0.000969
AC XY:
704
AN XY:
726880
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000448
Gnomad4 ASJ exome
AF:
0.0000767
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00132
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.000761
AC:
116
AN:
152372
Hom.:
0
Cov.:
33
AF XY:
0.000617
AC XY:
46
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00129
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000923
Hom.:
0
Bravo
AF:
0.000824
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.00208
AC:
8
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.000469
AC:
57
EpiCase
AF:
0.000763
EpiControl
AF:
0.000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.274C>T (p.H92Y) alteration is located in exon 2 (coding exon 2) of the DISP2 gene. This alteration results from a C to T substitution at nucleotide position 274, causing the histidine (H) at amino acid position 92 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T
Eigen
Benign
0.16
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.042
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.013
D
Polyphen
0.89
P
Vest4
0.45
MVP
0.26
MPC
0.74
ClinPred
0.078
T
GERP RS
5.2
Varity_R
0.14
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146107339; hg19: chr15-40655980; API