Variant chr13-106495811-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004093.4(EFNB2):c.436G>A(p.Asp146Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EFNB2
NM_004093.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

EFNB2 (HGNC:3227): (ephrin B2) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. [provided by RefSeq, Jul 2008]

EFNB2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33717418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EFNB2	NM_004093.4 linkuse as main transcript	c.436G>A	p.Asp146Asn	missense_variant	3/5	ENST00000646441.1
EFNB2	NM_001372057.1 linkuse as main transcript	c.436G>A	p.Asp146Asn	missense_variant	3/4
EFNB2	XM_017020406.3 linkuse as main transcript	c.442G>A	p.Asp148Asn	missense_variant	3/5
EFNB2	NM_001372056.1 linkuse as main transcript	c.407-817G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1 linkuse as main transcript	c.436G>A	p.Asp146Asn	missense_variant	3/5		NM_004093.4	P1
	ENST00000646480.1 linkuse as main transcript	n.496+2933C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

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

Mar 30, 2024

The c.436G>A (p.D146N) alteration is located in exon 3 (coding exon 3) of the EFNB2 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the aspartic acid (D) at amino acid position 146 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

0.077

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

D;D

Eigen

Benign

0.064

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.5

D;.

REVEL

Uncertain

0.32

Sift

Benign

0.057

T;.

Sift4G

Benign

0.26

T;.

Polyphen

0.0010

B;B

Vest4

0.22

MutPred

0.32

Gain of disorder (P = 0.2385);Gain of disorder (P = 0.2385);

MVP

0.82

MPC

0.60

ClinPred

0.94

GERP RS

5.5

Varity_R

0.62

gMVP

0.83

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over