20-46367543-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_133171.5(ELMO2):c.1980T>C(p.Asp660=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,612,608 control chromosomes in the GnomAD database, including 801,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (73889 hom., cov: 30)
  • Exomes 𝑓: 1.0 (728080 hom.)
• Consequence: ELMO2 NM_133171.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 20-46367543-A-G is Benign according to our data. Variant chr20-46367543-A-G is described in ClinVar as [Benign]. Clinvar id is 1236006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46367543-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELMO2	NM_133171.5	c.1980T>C	p.Asp660=	synonymous_variant	22/22	ENST00000290246.11
LOC124904917	XR_007067614.1	n.182+2823A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELMO2	ENST00000290246.11	c.1980T>C	p.Asp660=	synonymous_variant	22/22	1	NM_133171.5	P4
	ENST00000651935.1	n.151+2823A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149845 AN: 152106 Hom.: 73838 Cov.: 30

Gnomad AFR AF: 0.948

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

GnomAD3 exomes AF: 0.996 AC: 247133 AN: 248120 Hom.: 123098 AF XY: 0.997 AC XY: 133920 AN XY: 134324

Gnomad AFR exome AF: 0.946

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1458216 AN: 1460384 Hom.: 728080 Cov.: 50 AF XY: 0.999 AC XY: 725546 AN XY: 726496

Gnomad4 AFR exome AF: 0.949

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.997

GnomAD4 genome AF: 0.985 AC: 149955 AN: 152224 Hom.: 73889 Cov.: 30 AF XY: 0.986 AC XY: 73367 AN XY: 74420

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.995

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.988

Alfa AF: 0.996 Hom.: 85370

Bravo AF: 0.983

Asia WGS AF: 0.997 AC: 3466 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary intraosseous venous malformation Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.022
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2257495; hg19: chr20-44996182;