2-62990744-G-T

Variant names:

• chr2-62990744-G-T
• NM_001142616.3:c.2637G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142616.3(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. 14/22 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 NM_001142616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	NM_001142616.3	MANE Select	c.2637G>T	p.Lys879Asn	missense	Exon 16 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.2850G>T	p.Lys950Asn	missense	Exon 18 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.2850G>T	p.Lys950Asn	missense	Exon 18 of 25	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.2637G>T	p.Lys879Asn	missense	Exon 16 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.2850G>T	p.Lys950Asn	missense	Exon 18 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.2745G>T	p.Lys915Asn	missense	Exon 16 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Benign	0.073	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	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
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr2-63217879;