20-46375149-T-C

Variant names:

• chr20-46375149-T-C
• rs2257545
• NM_133171.5:c.1065+87A>G

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.1065+87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,513,318 control chromosomes in the GnomAD database, including 619,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (51862 hom., cov: 32)
  • Exomes 𝑓: 0.91 (567365 hom.)
• Consequence: ELMO2 NM_133171.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.424
• Publications: 3 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), G2P, Orphanet
• 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=-0.9).
• BP6: Variant 20-46375149-T-C is Benign according to our data. Variant chr20-46375149-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO2	NM_133171.5	MANE Select	c.1065+87A>G		intron	N/A	NP_573403.1
	ELMO2	NM_182764.3		c.1065+87A>G		intron	N/A	NP_877496.1
	ELMO2	NM_001318253.2		c.801+87A>G		intron	N/A	NP_001305182.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO2	ENST00000290246.11	TSL:1 MANE Select	c.1065+87A>G		intron	N/A	ENSP00000290246.6
	ELMO2	ENST00000396391.5	TSL:1	c.1065+87A>G		intron	N/A	ENSP00000379673.1
	ELMO2	ENST00000372176.5	TSL:5	c.801+87A>G		intron	N/A	ENSP00000361249.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122134 AN: 151950 Hom.: 51855 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.910 AC: 1238762 AN: 1361250 Hom.: 567365 AF XY: 0.911 AC XY: 611237 AN XY: 670610

African (AFR) AF: 0.487 AC: 15050 AN: 30884

American (AMR) AF: 0.916 AC: 32432 AN: 35418

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 20178 AN: 21452

East Asian (EAS) AF: 0.759 AC: 29520 AN: 38906

South Asian (SAS) AF: 0.913 AC: 68570 AN: 75116

European-Finnish (FIN) AF: 0.960 AC: 38063 AN: 39660

Middle Eastern (MID) AF: 0.909 AC: 3705 AN: 4078

European-Non Finnish (NFE) AF: 0.926 AC: 981216 AN: 1059398

Other (OTH) AF: 0.888 AC: 50028 AN: 56338

GnomAD4 genome AF: 0.803 AC: 122169 AN: 152068 Hom.: 51862 Cov.: 32 AF XY: 0.808 AC XY: 60112 AN XY: 74352

African (AFR) AF: 0.500 AC: 20697 AN: 41390

American (AMR) AF: 0.885 AC: 13527 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3286 AN: 3472

East Asian (EAS) AF: 0.757 AC: 3896 AN: 5150

South Asian (SAS) AF: 0.899 AC: 4335 AN: 4820

European-Finnish (FIN) AF: 0.961 AC: 10205 AN: 10620

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63309 AN: 68008

Other (OTH) AF: 0.831 AC: 1755 AN: 2112

Alfa AF: 0.865 Hom.: 12628

Bravo AF: 0.783

Asia WGS AF: 0.805 AC: 2801 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.42
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: rs2257545; hg19: chr20-45003788; COSMIC: COSV51681402; COSMIC: COSV51681402;