Variant chr15-40364523-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_033510.3(DISP2):c.582C>T(p.Pro194Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 1,613,772 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 51 hom. )

Consequence

DISP2
NM_033510.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.89

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:

LOC124903472 (HGNC:):

LOC124903472 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 15-40364523-C-T is Benign according to our data. Variant chr15-40364523-C-T is described in ClinVar as [Benign]. Clinvar id is 720007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1719/152330) while in subpopulation AFR AF= 0.0253 (1051/41566). AF 95% confidence interval is 0.024. There are 14 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP2	NM_033510.3 linkuse as main transcript	c.582C>T	p.Pro194Pro	synonymous_variant	4/8	ENST00000267889.5	NP_277045.1
LOC124903472	XR_007064597.1 linkuse as main transcript	n.2418-1386G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISP2	ENST00000267889.5 linkuse as main transcript	c.582C>T	p.Pro194Pro	synonymous_variant	4/8	1	NM_033510.3	ENSP00000267889.3		A7MBM2

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1718

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00713

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00563

AC:

1413

AN:

250848

Hom.:

AF XY:

0.00523

AC XY:

709

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00350

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00741

AC:

10822

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

5097

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00386

Gnomad4 NFE exome

AF:

0.00828

Gnomad4 OTH exome

AF:

0.00652

GnomAD4 genome

AF:

0.0113

AC:

1719

AN:

152330

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.00713

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00998

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00723

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.33

DANN

Benign

0.80

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over