15-40363902-C-T

Variant names:

• chr15-40363902-C-T
• rs150939222
• NM_033510.3:c.397C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033510.3(DISP2):​c.397C>T​(p.Arg133Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000958 in 1,565,972 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: DISP2 NM_033510.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• Publications: 1 publications found

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]

LOC124903472 (HGNC:):

ACMG classification

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=0.107943416).

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.397C>T	p.Arg133Cys	missense	Exon 2 of 8	NP_277045.1	A7MBM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISP2	ENST00000267889.5	TSL:1 MANE Select	c.397C>T	p.Arg133Cys	missense	Exon 2 of 8	ENSP00000267889.3	A7MBM2
	DISP2	ENST00000949525.1		c.397C>T	p.Arg133Cys	missense	Exon 2 of 8	ENSP00000619584.1
	DISP2	ENST00000949524.1		c.397C>T	p.Arg133Cys	missense	Exon 2 of 8	ENSP00000619583.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000468 AC: 10 AN: 213526 AF XY: 0.0000613

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000827

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.0000983 AC: 139 AN: 1413734 Hom.: 0 Cov.: 35 AF XY: 0.000100 AC XY: 70 AN XY: 697548

African (AFR) AF: 0.00 AC: 0 AN: 32414

American (AMR) AF: 0.0000496 AC: 2 AN: 40338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39142

South Asian (SAS) AF: 0.0000251 AC: 2 AN: 79648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.000116 AC: 126 AN: 1085630

Other (OTH) AF: 0.000154 AC: 9 AN: 58258

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74374

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000578 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.030	D
Polyphen		0.97	D
Vest4		0.19
MVP		0.22
MPC		0.52
ClinPred		0.31	T
GERP RS		0.78
Varity_R		0.092
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs150939222; hg19: chr15-40656103;