2-62990744-G-T

Position:

• chr2-62990744-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000431489.6(EHBP1):​c.2637G>T​(p.Lys879Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EHBP1 ENST00000431489.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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]

EHBP1-AS1 (HGNC:55766): (EHBP1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065134704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.2637G>T	p.Lys879Asn	missense_variant	16/23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.2637G>T	p.Lys879Asn	missense_variant	16/23	1	NM_001142616.3	ENSP00000403783	A1
EHBP1-AS1	ENST00000650490.1	n.572+22815C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 19, 2024

The c.2850G>T (p.K950N) alteration is located in exon 18 (coding exon 17) of the EHBP1 gene. This alteration results from a G to T substitution at nucleotide position 2850, causing the lysine (K) at amino acid position 950 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	0.38
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;.;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	.;.;L;.
MutationTaster	Benign	0.73	D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.073	T;T;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.26
MutPred		0.14		.;.;Loss of ubiquitination at K950 (P = 0.0116);.;
MVP		0.49
MPC		0.13
ClinPred		0.42	T
GERP RS		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.48

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: chr2-63217879;