chr22-37373527-G-C

Position:

• chr22-37373527-G-C

Variant summary

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

The NM_052906.5(ELFN2):​c.2008C>G​(p.Leu670Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.0e-7 (0 hom.)
• Consequence: ELFN2 NM_052906.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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]

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=0.08144671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELFN2	NM_052906.5	c.2008C>G	p.Leu670Val	missense_variant	3/3	ENST00000402918.7
ELFN2	NR_110512.2	n.183-30824C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELFN2	ENST00000402918.7	c.2008C>G	p.Leu670Val	missense_variant	3/3	4	NM_052906.5	P1
ELFN2	ENST00000452946.1	n.149-30824C>G		intron_variant, non_coding_transcript_variant		4
ELFN2	ENST00000430883.5	n.434+11323C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000112 AC: 2 AN: 178866 Hom.: 0 AF XY: 0.0000204 AC XY: 2 AN XY: 98124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000363

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000389

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422420 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 704460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000841 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.060	N;.
REVEL	Benign	0.085
Sift	Benign	0.52	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.28	B;B
Vest4		0.082
MutPred		0.051		Gain of methylation at K666 (P = 0.0566);Gain of methylation at K666 (P = 0.0566);
MVP		0.41
MPC		0.65
ClinPred		0.094	T
GERP RS		4.7
Varity_R		0.18
gMVP		0.10

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: rs769989620; hg19: chr22-37769567;