dbSNP rs2609359: DISP1:c.890-14T>C (chr1-222994871-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377229.1(DISP1):c.890-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,572,070 control chromosomes in the GnomAD database, including 84,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9733 hom., cov: 32)

Exomes 𝑓: 0.32 ( 74706 hom. )

Consequence

DISP1
NM_001377229.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0770

Publications

6 publications found

Variant links:

Genes affected

DISP1 (HGNC:19711): (dispatched RND transporter family member 1) The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]

DISP1 Gene-Disease associations (from GenCC):

holoprosencephaly
Inheritance: SD, AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, ClinGen, Orphanet

DISP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-222994871-T-C is Benign according to our data. Variant chr1-222994871-T-C is described in ClinVar as Benign. ClinVar VariationId is 262132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377229.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DISP1	NM_001377229.1	MANE Select	c.890-14T>C	intron	N/A	NP_001364158.1	Q96F81
DISP1	NM_001369594.1		c.890-14T>C	intron	N/A	NP_001356523.1	Q96F81
DISP1	NM_001377228.1		c.890-14T>C	intron	N/A	NP_001364157.1	Q96F81

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DISP1	ENST00000675850.1	MANE Select	c.890-14T>C	intron	N/A	ENSP00000502357.1	Q96F81
DISP1	ENST00000284476.7	TSL:1	c.890-14T>C	intron	N/A	ENSP00000284476.6	Q96F81
DISP1	ENST00000900747.1		c.890-14T>C	intron	N/A	ENSP00000570806.1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53280

AN:

151808

Hom.:

9713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.344

AC:

85707

AN:

249154

AF XY:

0.347

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.319

AC:

452437

AN:

1420144

Hom.:

74706

Cov.:

AF XY:

0.322

AC XY:

228138

AN XY:

709418

show subpopulations

African (AFR)

AF:

0.428

AC:

13906

AN:

32500

American (AMR)

AF:

0.369

AC:

16418

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

7473

AN:

25866

East Asian (EAS)

AF:

0.282

AC:

11103

AN:

39418

South Asian (SAS)

AF:

0.451

AC:

38407

AN:

85118

European-Finnish (FIN)

AF:

0.356

AC:

18606

AN:

52330

Middle Eastern (MID)

AF:

0.272

AC:

1417

AN:

5216

European-Non Finnish (NFE)

AF:

0.303

AC:

325905

AN:

1076252

Other (OTH)

AF:

0.326

AC:

19202

AN:

58948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

14709

29418

44128

58837

73546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10806

21612

32418

43224

54030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

53346

AN:

151926

Hom.:

9733

Cov.:

AF XY:

0.355

AC XY:

26383

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.436

AC:

18059

AN:

41426

American (AMR)

AF:

0.338

AC:

5148

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

986

AN:

3466

East Asian (EAS)

AF:

0.296

AC:

1532

AN:

5180

South Asian (SAS)

AF:

0.446

AC:

2139

AN:

4798

European-Finnish (FIN)

AF:

0.376

AC:

3961

AN:

10522

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20336

AN:

67976

Other (OTH)

AF:

0.328

AC:

691

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1725

3449

5174

6898

8623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

1265

Bravo

AF:

0.352

Asia WGS

AF:

0.408

AC:

1419

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

(source)

DANN

Benign

0.84

PhyloP100

0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over