rs373613614

Variant names:

• chr2-200988282-C-A
• rs373613614
• NM_001321623.1:c.971G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-200988282-C-A
• chr2-200988282-C-G
• chr2-200988282-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001321623.1(HYCC2):​c.971G>T​(p.Arg324Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R324H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HYCC2 NM_001321623.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29
• Publications: 0 publications found

Genes affected

HYCC2 (HGNC:28593): (hyccin PI4KA lipid kinase complex subunit 2) Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000183308 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321623.1. 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
	HYCC2	NM_001321623.1	MANE Select	c.971G>T	p.Arg324Leu	missense	Exon 11 of 13	NP_001308552.1	A0A804HIT6
	HYCC2	NM_001321624.1		c.971G>T	p.Arg324Leu	missense	Exon 10 of 12	NP_001308553.1	A0A804HIT6
	HYCC2	NM_001321625.2		c.971G>T	p.Arg324Leu	missense	Exon 11 of 13	NP_001308554.1	A0A804HIT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC2	ENST00000681958.1	MANE Select	c.971G>T	p.Arg324Leu	missense	Exon 11 of 13	ENSP00000507218.1	A0A804HIT6
	HYCC2	ENST00000418596.7	TSL:1	c.971G>T	p.Arg324Leu	missense	Exon 11 of 12	ENSP00000393667.2	Q8IXS8
	HYCC2	ENST00000286181.7	TSL:1	n.*724G>T		non_coding_transcript_exon	Exon 12 of 14	ENSP00000286181.3	F8W7X4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459028 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725774

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110634

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.56
Sift	Benign	0.12	T
Sift4G	Uncertain	0.046	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.53		Loss of disorder (P = 0.0122)
MVP		0.44
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.62
Mutation Taster		=52/48	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

dbSNP: rs373613614; hg19: chr2-201853005;