20-46367615-C-A

Variant names:

• chr20-46367615-C-A
• rs2297058
• NM_133171.5:c.1963-55G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_133171.5(ELMO2):​c.1963-55G>T 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 1,455,170 control chromosomes in the GnomAD database, including 7,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2127 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5536 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.490
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 20-46367615-C-A is Benign according to our data. Variant chr20-46367615-C-A is described in ClinVar as Benign. ClinVar VariationId is 1269238.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.1963-55G>T		intron	N/A	NP_573403.1	Q96JJ3-1
	ELMO2	NM_182764.3		c.1963-55G>T		intron	N/A	NP_877496.1	Q96JJ3-1
	ELMO2	NM_001318253.2		c.1699-55G>T		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.1963-55G>T		intron	N/A	ENSP00000290246.6	Q96JJ3-1
	ELMO2	ENST00000396391.5	TSL:1	c.1963-55G>T		intron	N/A	ENSP00000379673.1	Q96JJ3-1
	ELMO2	ENST00000372176.5	TSL:5	c.1699-55G>T		intron	N/A	ENSP00000361249.1	Q96JJ3-3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20381 AN: 151968 Hom.: 2118 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0815 AC: 106204 AN: 1303082 Hom.: 5536 AF XY: 0.0807 AC XY: 52081 AN XY: 645624

African (AFR) AF: 0.298 AC: 8555 AN: 28688

American (AMR) AF: 0.0730 AC: 2356 AN: 32294

Ashkenazi Jewish (ASJ) AF: 0.0587 AC: 1232 AN: 20982

East Asian (EAS) AF: 0.195 AC: 7069 AN: 36318

South Asian (SAS) AF: 0.0819 AC: 5836 AN: 71248

European-Finnish (FIN) AF: 0.0410 AC: 2081 AN: 50802

Middle Eastern (MID) AF: 0.0798 AC: 419 AN: 5248

European-Non Finnish (NFE) AF: 0.0733 AC: 73509 AN: 1003192

Other (OTH) AF: 0.0948 AC: 5147 AN: 54310

GnomAD4 genome AF: 0.134 AC: 20422 AN: 152088 Hom.: 2127 Cov.: 32 AF XY: 0.130 AC XY: 9661 AN XY: 74350

African (AFR) AF: 0.291 AC: 12059 AN: 41406

American (AMR) AF: 0.0914 AC: 1399 AN: 15306

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

East Asian (EAS) AF: 0.186 AC: 958 AN: 5148

South Asian (SAS) AF: 0.0904 AC: 436 AN: 4822

European-Finnish (FIN) AF: 0.0388 AC: 412 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0685 AC: 4661 AN: 68004

Other (OTH) AF: 0.125 AC: 265 AN: 2116

Alfa AF: 0.110 Hom.: 268

Bravo AF: 0.145

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	-0.34
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		-0.49
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: rs2297058; hg19: chr20-44996254;