chr15-40363779-C-T

Variant names:

• chr15-40363779-C-T
• rs146107339
• NM_033510.3:c.274C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: DISP2 NM_033510.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07754001).

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.274C>T	p.His92Tyr	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.274C>T	p.His92Tyr	missense	Exon 2 of 8	ENSP00000267889.3	A7MBM2
	DISP2	ENST00000949525.1		c.274C>T	p.His92Tyr	missense	Exon 2 of 8	ENSP00000619584.1
	DISP2	ENST00000949524.1		c.274C>T	p.His92Tyr	missense	Exon 2 of 8	ENSP00000619583.1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152254 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000515 AC: 129 AN: 250576 AF XY: 0.000539

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 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

African (AFR) AF: 0.000149 AC: 5 AN: 33462

American (AMR) AF: 0.000448 AC: 20 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00132 AC: 1465 AN: 1111660

Other (OTH) AF: 0.000646 AC: 39 AN: 60356

GnomAD4 genome AF: 0.000761 AC: 116 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.000617 AC XY: 46 AN XY: 74512

African (AFR) AF: 0.000289 AC: 12 AN: 41592

American (AMR) AF: 0.000915 AC: 14 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00129 AC: 88 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000951 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

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	0.089
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
PhyloP100		2.2
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
Mutation Taster		=79/21	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: rs146107339; hg19: chr15-40655980;