NM_001321623.1:c.1625G>A

Variant names:

• chr2-200981406-C-T
• rs958575569
• NM_001321623.1:c.1625G>A

Variant summary

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

The NM_001321623.1(HYCC2):​c.1625G>A​(p.Arg542Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: HYCC2 NM_001321623.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• 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 2 ACMG points.

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

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.1625G>A	p.Arg542Gln	missense	Exon 13 of 13	NP_001308552.1	A0A804HIT6
	HYCC2	NM_001321624.1		c.1625G>A	p.Arg542Gln	missense	Exon 12 of 12	NP_001308553.1	A0A804HIT6
	HYCC2	NM_001321625.2		c.1625G>A	p.Arg542Gln	missense	Exon 13 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.1625G>A	p.Arg542Gln	missense	Exon 13 of 13	ENSP00000507218.1	A0A804HIT6
	HYCC2	ENST00000418596.7	TSL:1	c.1457G>A	p.Arg486Gln	missense	Exon 12 of 12	ENSP00000393667.2	Q8IXS8
	HYCC2	ENST00000286181.7	TSL:1	n.*1378G>A		non_coding_transcript_exon	Exon 14 of 14	ENSP00000286181.3	F8W7X4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727224

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	Benign	0.14
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.77
MVP		0.84
MPC		1.2
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.57
gMVP		0.61
Mutation Taster		=87/13	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: rs958575569; hg19: chr2-201846129; COSMIC: COSV53776128; COSMIC: COSV53776128;