2-62859244-A-G

Position:

• chr2-62859244-A-G

Variant summary

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

The NM_001142616.3(EHBP1):​c.710A>G​(p.Asp237Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60

Genes affected

EHBP1 (HGNC:29144): (EH domain binding protein 1) This gene encodes an Eps15 homology domain binding protein. The encoded protein may play a role in endocytic trafficking. A single nucleotide polymorphism in this gene is associated with an aggressive form of prostate cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

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=0.24314994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.710A>G	p.Asp237Gly	missense_variant	8/23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.710A>G	p.Asp237Gly	missense_variant	8/23	1	NM_001142616.3	ENSP00000403783	A1

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

May 17, 2023

The c.815A>G (p.D272G) alteration is located in exon 9 (coding exon 8) of the EHBP1 gene. This alteration results from a A to G substitution at nucleotide position 815, causing the aspartic acid (D) at amino acid position 272 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;T;.;T;.
Eigen	Benign	0.069
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	.;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.7	.;.;.;L;.
MutationTaster	Benign	0.58	D;D;D;D;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.019	D;T;D;D;D
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.14	B;.;B;B;B
Vest4		0.36
MutPred		0.12		.;.;.;Loss of stability (P = 0.1313);.;
MVP		0.56
MPC		0.15
ClinPred		0.83	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-63086379;