15-40364440-G-C

Variant names:

• chr15-40364440-G-C
• NM_033510.3:c.499G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033510.3(DISP2):​c.499G>C​(p.Glu167Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DISP2 NM_033510.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP2	NM_033510.3	c.499G>C	p.Glu167Gln	missense_variant	Exon 4 of 8	ENST00000267889.5	NP_277045.1
LOC124903472	XR_007064597.1	n.2418-1303C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP2	ENST00000267889.5	c.499G>C	p.Glu167Gln	missense_variant	Exon 4 of 8	1	NM_033510.3	ENSP00000267889.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.499G>C (p.E167Q) alteration is located in exon 4 (coding exon 4) of the DISP2 gene. This alteration results from a G to C substitution at nucleotide position 499, causing the glutamic acid (E) at amino acid position 167 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.030	D
Sift4G	Benign	0.068	T
Polyphen		0.98	D
Vest4		0.43
MutPred		0.49		Gain of MoRF binding (P = 0.2143);
MVP		0.42
MPC		1.1
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.21
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-40656641;