rs367945618

Variant names:

• chr22-37373665-C-T
• rs367945618
• NM_052906.5:c.1870G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052906.5(ELFN2):​c.1870G>A​(p.Val624Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,420,148 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: ELFN2 NM_052906.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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

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=0.23610196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN2	NM_052906.5	c.1870G>A	p.Val624Met	missense_variant	Exon 3 of 3	ENST00000402918.7	NP_443138.2
ELFN2	NR_110512.2	n.183-30962G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELFN2	ENST00000402918.7	c.1870G>A	p.Val624Met	missense_variant	Exon 3 of 3	4	NM_052906.5	ENSP00000385277.1
ELFN2	ENST00000430883.5	n.434+11185G>A		intron_variant	Intron 1 of 2	2
ELFN2	ENST00000452946.1	n.149-30962G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000422 AC: 6 AN: 1420148 Hom.: 0 Cov.: 30 AF XY: 0.00000284 AC XY: 2 AN XY: 703160

Gnomad4 AFR exome AF: 0.0000314

Gnomad4 AMR exome AF: 0.0000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1870G>A (p.V624M) 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 1870, causing the valine (V) at amino acid position 624 to be replaced by a methionine (M). 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	0.16
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.11
Sift	Benign	0.039	D;.
Sift4G	Uncertain	0.059	T;T
Polyphen		1.0	D;D
Vest4		0.34
MutPred		0.16		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.57
MPC		1.3
ClinPred		0.51	D
GERP RS		4.7
Varity_R		0.098
gMVP		0.15

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

Other links and lift over

dbSNP: rs367945618; hg19: chr22-37769705;