20-46370408-C-A

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.1884+35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,594,978 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (50 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

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=-0.87).
• BP6: Variant 20-46370408-C-A is Benign according to our data. Variant chr20-46370408-C-A is described in ClinVar as [Benign]. Clinvar id is 1227680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMO2	NM_133171.5	c.1884+35G>T		intron_variant		ENST00000290246.11
LOC124904917	XR_007067614.1	n.182+5688C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMO2	ENST00000290246.11	c.1884+35G>T		intron_variant		1	NM_133171.5	P4
	ENST00000651935.1	n.151+5688C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152214 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00496 AC: 1248 AN: 251442 Hom.: 25 AF XY: 0.00486 AC XY: 661 AN XY: 135898

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0589

Gnomad SAS exome AF: 0.00421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00178 AC: 2568 AN: 1442646 Hom.: 50 Cov.: 28 AF XY: 0.00187 AC XY: 1343 AN XY: 719048

Gnomad4 AFR exome AF: 0.000302

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0474

Gnomad4 SAS exome AF: 0.00454

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000302

Gnomad4 OTH exome AF: 0.00418

GnomAD4 genome AF: 0.00253 AC: 386 AN: 152332 Hom.: 9 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74492

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000616 Hom.: 0

Bravo AF: 0.00265

Asia WGS AF: 0.0340 AC: 119 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.0
Dann	Benign	0.90

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: rs147381414; hg19: chr20-44999047; COSMIC: COSV51683175; COSMIC: COSV51683175;