rs781726017

Variant names:

• chr22-37373590-C-G
• rs781726017
• NM_052906.5:c.1945G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-37373590-C-G
• chr22-37373590-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052906.5(ELFN2):​c.1945G>C​(p.Asp649His) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELFN2 NM_052906.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 1 publications found

Genes affected

ELFN2 (HGNC:29396): (extracellular leucine rich repeat and fibronectin type III domain containing 2) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ELFN2 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34693885).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052906.5. 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
	ELFN2	NM_052906.5	MANE Select	c.1945G>C	p.Asp649His	missense	Exon 3 of 3	NP_443138.2	Q5R3F8
	ELFN2	NR_110512.2		n.183-30887G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN2	ENST00000402918.7	TSL:4 MANE Select	c.1945G>C	p.Asp649His	missense	Exon 3 of 3	ENSP00000385277.1	Q5R3F8
	ELFN2	ENST00000939364.1		c.1945G>C	p.Asp649His	missense	Exon 2 of 2	ENSP00000609423.1
	ELFN2	ENST00000939365.1		c.1945G>C	p.Asp649His	missense	Exon 4 of 4	ENSP00000609424.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455188 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723622

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.00 AC: 0 AN: 85474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110114

Other (OTH) AF: 0.00 AC: 0 AN: 60078

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.21
Sift	Uncertain	0.015	D
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.16		Loss of sheet (P = 0.0817)
MVP		0.59
MPC		1.7
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.22
gMVP		0.33
Mutation Taster		=69/31	polymorphism

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: rs781726017; hg19: chr22-37769630;