20-46369063-C-T

Variant names:

• chr20-46369063-C-T
• rs2297055
• NM_133171.5:c.1885-95G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133171.5(ELMO2):​c.1885-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,116,122 control chromosomes in the GnomAD database, including 6,401 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: 0.081 (4268 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• primary intraosseous venous malformation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Ramon syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000273828 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-46369063-C-T is Benign according to our data. Variant chr20-46369063-C-T is described in ClinVar as Benign. ClinVar VariationId is 1183768.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO2	NM_133171.5	MANE Select	c.1885-95G>A		intron	N/A	NP_573403.1	Q96JJ3-1
	ELMO2	NM_182764.3		c.1885-95G>A		intron	N/A	NP_877496.1	Q96JJ3-1
	ELMO2	NM_001318253.2		c.1621-95G>A		intron	N/A	NP_001305182.1	Q96JJ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO2	ENST00000290246.11	TSL:1 MANE Select	c.1885-95G>A		intron	N/A	ENSP00000290246.6	Q96JJ3-1
	ELMO2	ENST00000396391.5	TSL:1	c.1885-95G>A		intron	N/A	ENSP00000379673.1	Q96JJ3-1
	ELMO2	ENST00000372176.5	TSL:5	c.1621-95G>A		intron	N/A	ENSP00000361249.1	Q96JJ3-3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20409 AN: 152018 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0812 AC: 78257 AN: 963986 Hom.: 4268 Cov.: 13 AF XY: 0.0805 AC XY: 40105 AN XY: 498054

African (AFR) AF: 0.294 AC: 6904 AN: 23448

American (AMR) AF: 0.0720 AC: 2957 AN: 41054

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 1301 AN: 21684

East Asian (EAS) AF: 0.195 AC: 7193 AN: 36930

South Asian (SAS) AF: 0.0810 AC: 5933 AN: 73242

European-Finnish (FIN) AF: 0.0409 AC: 2051 AN: 50184

Middle Eastern (MID) AF: 0.0796 AC: 295 AN: 3708

European-Non Finnish (NFE) AF: 0.0709 AC: 47498 AN: 670082

Other (OTH) AF: 0.0945 AC: 4125 AN: 43654

GnomAD4 genome AF: 0.134 AC: 20450 AN: 152136 Hom.: 2133 Cov.: 32 AF XY: 0.130 AC XY: 9677 AN XY: 74386

African (AFR) AF: 0.292 AC: 12083 AN: 41448

American (AMR) AF: 0.0914 AC: 1397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3470

East Asian (EAS) AF: 0.187 AC: 968 AN: 5170

South Asian (SAS) AF: 0.0907 AC: 438 AN: 4828

European-Finnish (FIN) AF: 0.0388 AC: 412 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0685 AC: 4657 AN: 68004

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.110 Hom.: 326

Bravo AF: 0.146

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.81
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2297055; hg19: chr20-44997702; COSMIC: COSV51682863; COSMIC: COSV51682863;