20-46370638-A-G

Position:

• chr20-46370638-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133171.5(ELMO2):​c.1802-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 962,928 control chromosomes in the GnomAD database, including 5,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2133 hom., cov: 32)
  • Exomes 𝑓: 0.084 (3703 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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]

ELMO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-46370638-A-G is Benign according to our data. Variant chr20-46370638-A-G is described in ClinVar as [Benign]. Clinvar id is 1266268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMO2	NM_133171.5	c.1802-113T>C		intron_variant		ENST00000290246.11	NP_573403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMO2	ENST00000290246.11	c.1802-113T>C		intron_variant		1	NM_133171.5	ENSP00000290246.6
ELMO2	ENST00000372176.5	c.1538-113T>C		intron_variant		5		ENSP00000361249.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20430 AN: 152042 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0837 AC: 67832 AN: 810768 Hom.: 3703 AF XY: 0.0826 AC XY: 35341 AN XY: 427852

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0726

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.0813

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.0732

Gnomad4 OTH exome AF: 0.0958

GnomAD4 genome AF: 0.135 AC: 20471 AN: 152160 Hom.: 2133 Cov.: 32 AF XY: 0.130 AC XY: 9687 AN XY: 74414

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0686

Gnomad4 OTH AF: 0.124

Alfa AF: 0.100 Hom.: 181

Bravo AF: 0.146

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.90
CADD	Benign	0.74
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs2297054; hg19: chr20-44999277; COSMIC: COSV51681970; COSMIC: COSV51681970;