Genetic Variant ELFN2:p.Asp660Asn (chr22-37373557-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052906.5(ELFN2):c.1978G>A(p.Asp660Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,599,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ELFN2
NM_052906.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

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 links:

ELFN2 (HGNC:):

ELFN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2531036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN2	NM_052906.5 link	c.1978G>A	p.Asp660Asn	missense_variant	Exon 3 of 3	ENST00000402918.7	NP_443138.2	Q5R3F8
ELFN2	NR_110512.2 link	n.183-30854G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELFN2	ENST00000402918.7 link	c.1978G>A	p.Asp660Asn	missense_variant	Exon 3 of 3	4	NM_052906.5	ENSP00000385277.1	Q5R3F8
ELFN2	ENST00000430883.5 link	n.434+11293G>A		intron_variant	Intron 1 of 2	2
ELFN2	ENST00000452946.1 link	n.149-30854G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1447420

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

719016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000498

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1978G>A (p.D660N) alteration is located in exon 3 (coding exon 1) of the ELFN2 gene. This alteration results from a G to A substitution at nucleotide position 1978, causing the aspartic acid (D) at amino acid position 660 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.092

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.017

D;D

Polyphen

0.99

D;D

Vest4

0.21

MutPred

0.15

Loss of ubiquitination at K662 (P = 0.0371);Loss of ubiquitination at K662 (P = 0.0371);

MVP

0.58

MPC

1.1

ClinPred

0.82

GERP RS

4.7

Varity_R

0.19

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over