Variant 22-37373464-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052906.5(ELFN2):c.2071G>A(p.Gly691Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ELFN2
NM_052906.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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:

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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=0.07763186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELFN2	NM_052906.5 link	c.2071G>A	p.Gly691Ser	missense_variant	3/3	ENST00000402918.7	NP_443138.2	Q5R3F8
ELFN2	NR_110512.2 link	n.183-30761G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELFN2	ENST00000402918.7 link	c.2071G>A	p.Gly691Ser	missense_variant	3/3	4	NM_052906.5	ENSP00000385277.1	Q5R3F8
ELFN2	ENST00000430883.5 link	n.434+11386G>A		intron_variant		2
ELFN2	ENST00000452946.1 link	n.149-30761G>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380444

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000252

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.2071G>A (p.G691S) 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 2071, causing the glycine (G) at amino acid position 691 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.12

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.26

N;.

REVEL

Benign

0.051

Sift

Benign

0.17

T;.

Sift4G

Uncertain

0.059

T;T

Polyphen

0.0

B;B

Vest4

0.27

MutPred

0.22

Gain of glycosylation at G691 (P = 0.0015);Gain of glycosylation at G691 (P = 0.0015);

MVP

0.38

MPC

0.78

ClinPred

0.071

GERP RS

2.1

Varity_R

0.044

gMVP

0.26

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