19-12763412-C-A

Variant names:

• chr19-12763412-C-A
• rs200083706
• NM_013312.3:c.2030G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013312.3(HOOK2):​c.2030G>T​(p.Arg677Leu) 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. 12/21 in silico tools predict a benign 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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

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=0.3034152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOOK2	NM_013312.3	c.2030G>T	p.Arg677Leu	missense_variant	Exon 23 of 23	ENST00000397668.8	NP_037444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOOK2	ENST00000397668.8	c.2030G>T	p.Arg677Leu	missense_variant	Exon 23 of 23	1	NM_013312.3	ENSP00000380785.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.085
Sift	Benign	0.37	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.54		Loss of MoRF binding (P = 0.0294);.;
MVP		0.35
MPC		0.48
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.099
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200083706; hg19: chr19-12874226;