15-40370547-G-C

Variant names:

• chr15-40370547-G-C
• rs3803359
• NM_033510.3:c.*229G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033510.3(DISP2):​c.*229G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 640,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: DISP2 NM_033510.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 13 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP2	NM_033510.3	c.*229G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000267889.5	NP_277045.1
LOC124903472	XR_007064597.1	n.2417+336C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP2	ENST00000267889.5	c.*229G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_033510.3	ENSP00000267889.3
DISP2	ENST00000558623.1	n.75-65G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000156 AC: 1 AN: 640826 Hom.: 0 Cov.: 8 AF XY: 0.00000294 AC XY: 1 AN XY: 339794

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17440

American (AMR) AF: 0.00 AC: 0 AN: 34058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20244

East Asian (EAS) AF: 0.00 AC: 0 AN: 31186

South Asian (SAS) AF: 0.00 AC: 0 AN: 63658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4208

European-Non Finnish (NFE) AF: 0.00000247 AC: 1 AN: 405100

Other (OTH) AF: 0.00 AC: 0 AN: 33282

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.77
PhyloP100		1.1

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: rs3803359; hg19: chr15-40662748;