NM_013312.3:c.1969G>T

Variant names:

• chr19-12763569-C-A
• rs189241336
• NM_013312.3:c.1969G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013312.3(HOOK2):​c.1969G>T​(p.Glu657*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOOK2 NM_013312.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• Publications: 17 publications found

Genes affected

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013312.3. 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
	HOOK2	NM_013312.3	MANE Select	c.1969G>T	p.Glu657*	stop_gained	Exon 22 of 23	NP_037444.2	Q96ED9-1
	HOOK2	NM_001400041.1		c.2071G>T	p.Glu691*	stop_gained	Exon 21 of 22	NP_001386970.1
	HOOK2	NM_001100176.2		c.1963G>T	p.Glu655*	stop_gained	Exon 21 of 22	NP_001093646.1	Q96ED9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOOK2	ENST00000397668.8	TSL:1 MANE Select	c.1969G>T	p.Glu657*	stop_gained	Exon 22 of 23	ENSP00000380785.2	Q96ED9-1
	HOOK2	ENST00000264827.9	TSL:1	c.1963G>T	p.Glu655*	stop_gained	Exon 21 of 22	ENSP00000264827.4	Q96ED9-2
	HOOK2	ENST00000894580.1		c.2257G>T	p.Glu753*	stop_gained	Exon 21 of 22	ENSP00000564639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 20

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		5.1
Vest4		0.17
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=16/184	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs189241336; hg19: chr19-12874383;