chr22-37373317-C-T

Position:

• chr22-37373317-C-T

Variant summary

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

The NM_052906.5(ELFN2):​c.2218G>A​(p.Asp740Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELFN2 NM_052906.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELFN2	NM_052906.5	c.2218G>A	p.Asp740Asn	missense_variant	3/3	ENST00000402918.7
ELFN2	NR_110512.2	n.183-30614G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELFN2	ENST00000402918.7	c.2218G>A	p.Asp740Asn	missense_variant	3/3	4	NM_052906.5	P1
ELFN2	ENST00000452946.1	n.149-30614G>A		intron_variant, non_coding_transcript_variant		4
ELFN2	ENST00000430883.5	n.434+11533G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.2218G>A (p.D740N) 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 2218, causing the aspartic acid (D) at amino acid position 740 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.56
MutPred		0.23		Gain of MoRF binding (P = 0.0403);Gain of MoRF binding (P = 0.0403);
MVP		0.59
MPC		1.6
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.54
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37769357;