rs2072994

Variant names:

• chr1-11519413-G-A
• rs2072994
• NM_020780.2:c.1948G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_020780.2(DISP3):​c.1948G>A​(p.Ala650Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,438 control chromosomes in the GnomAD database, including 287,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A650S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.47 (20740 hom., cov: 32)
  • Exomes 𝑓: 0.59 (266985 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.522
• Publications: 26 publications found

Genes affected

DISP3 (HGNC:29251): (dispatched RND transporter family member 3) Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.6140498E-6).
• BP6: Variant 1-11519413-G-A is Benign according to our data. Variant chr1-11519413-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060671.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020780.2. 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
	DISP3	NM_020780.2	MANE Select	c.1948G>A	p.Ala650Thr	missense	Exon 8 of 21	NP_065831.1	Q9P2K9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISP3	ENST00000294484.7	TSL:1 MANE Select	c.1948G>A	p.Ala650Thr	missense	Exon 8 of 21	ENSP00000294484.6	Q9P2K9-1
	DISP3	ENST00000922105.1		c.2062G>A	p.Ala688Thr	missense	Exon 8 of 21	ENSP00000592164.1
	DISP3	ENST00000922103.1		c.1948G>A	p.Ala650Thr	missense	Exon 8 of 21	ENSP00000592162.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71608 AN: 151894 Hom.: 20735 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.484

GnomAD2 exomes AF: 0.555 AC: 138471 AN: 249316 AF XY: 0.552

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.593 AC: 866949 AN: 1461426 Hom.: 266985 Cov.: 68 AF XY: 0.588 AC XY: 427632 AN XY: 727030

African (AFR) AF: 0.118 AC: 3937 AN: 33476

American (AMR) AF: 0.715 AC: 31953 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14073 AN: 26128

East Asian (EAS) AF: 0.256 AC: 10159 AN: 39698

South Asian (SAS) AF: 0.410 AC: 35392 AN: 86248

European-Finnish (FIN) AF: 0.646 AC: 34297 AN: 53102

Middle Eastern (MID) AF: 0.534 AC: 3081 AN: 5768

European-Non Finnish (NFE) AF: 0.630 AC: 700474 AN: 1111916

Other (OTH) AF: 0.556 AC: 33583 AN: 60376

GnomAD4 genome AF: 0.471 AC: 71624 AN: 152012 Hom.: 20740 Cov.: 32 AF XY: 0.470 AC XY: 34917 AN XY: 74304

African (AFR) AF: 0.134 AC: 5541 AN: 41484

American (AMR) AF: 0.624 AC: 9525 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1384 AN: 5148

South Asian (SAS) AF: 0.385 AC: 1852 AN: 4808

European-Finnish (FIN) AF: 0.634 AC: 6697 AN: 10566

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42959 AN: 67956

Other (OTH) AF: 0.483 AC: 1017 AN: 2106

Alfa AF: 0.586 Hom.: 79172

Bravo AF: 0.461

TwinsUK AF: 0.628 AC: 2327

ALSPAC AF: 0.605 AC: 2330

ESP6500AA AF: 0.140 AC: 566

ESP6500EA AF: 0.616 AC: 5141

ExAC AF: 0.543 AC: 65682

Asia WGS AF: 0.307 AC: 1067 AN: 3478

EpiCase AF: 0.612

EpiControl AF: 0.618

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DISP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.11
DANN	Benign	0.24
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0000036	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.52
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.12
Sift	Benign	0.66	T
Sift4G	Benign	0.83	T
Polyphen		0.0040	B
Vest4		0.0090
MPC		0.36
ClinPred		0.0052	T
GERP RS		-5.8
Varity_R		0.028
gMVP		0.32
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072994; hg19: chr1-11579470; COSMIC: COSV53820610;