20-46371319-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133171.5(ELMO2):c.1801+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,605,666 control chromosomes in the GnomAD database, including 8,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2179 hom., cov: 33)
  • Exomes 𝑓: 0.082 (6267 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.402

Genes affected

ELMO2 (HGNC:17233): (engulfment and cell motility 2) The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein. Similarity to a C. elegans protein suggests that this protein may function in phagocytosis of apoptotic cells and in cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-46371319-A-G is Benign according to our data. Variant chr20-46371319-A-G is described in ClinVar as [Benign]. Clinvar id is 1280831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMO2	NM_133171.5	c.1801+33T>C		intron_variant		ENST00000290246.11
LOC124904917	XR_007067614.1	n.182+6599A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMO2	ENST00000290246.11	c.1801+33T>C		intron_variant		1	NM_133171.5	P4
	ENST00000651935.1	n.151+6599A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20591 AN: 152166 Hom.: 2170 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.0918 AC: 23006 AN: 250536 Hom.: 1598 AF XY: 0.0875 AC XY: 11845 AN XY: 135404

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.0678

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.0841

Gnomad FIN exome AF: 0.0413

Gnomad NFE exome AF: 0.0711

Gnomad OTH exome AF: 0.0795

GnomAD4 exome AF: 0.0820 AC: 119111 AN: 1453382 Hom.: 6267 Cov.: 29 AF XY: 0.0810 AC XY: 58573 AN XY: 723530

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.0820

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0734

Gnomad4 OTH exome AF: 0.0950

GnomAD4 genome AF: 0.135 AC: 20633 AN: 152284 Hom.: 2179 Cov.: 33 AF XY: 0.131 AC XY: 9764 AN XY: 74478

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0686

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0940 Hom.: 287

Bravo AF: 0.147

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.90
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Publications

LitVar

Other links and lift over

dbSNP: rs6090483; hg19: chr20-44999958; COSMIC: COSV51681981; COSMIC: COSV51681981;