rs749172950

Variant names:

• chr16-55566953-A-G
• rs749172950
• NM_032330.3:c.197A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032330.3(CAPNS2):​c.197A>G​(p.His66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CAPNS2 NM_032330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 0 publications found

Genes affected

CAPNS2 (HGNC:16371): (calpain small subunit 2) Enables calcium-dependent cysteine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LPCAT2 (HGNC:26032): (lysophosphatidylcholine acyltransferase 2) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded enzyme may function in two ways: to catalyze the biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) from 1-O-alkyl-sn-glycero-3-phosphocholine, and to catalyze the synthesis of glycerophospholipid precursors from arachidonyl-CoA and lysophosphatidylcholine. The encoded protein may function in membrane biogenesis and production of platelet-activating factor in inflammatory cells. The enzyme may localize to the endoplasmic reticulum and the Golgi. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22347775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032330.3. 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
	CAPNS2	NM_032330.3	MANE Select	c.197A>G	p.His66Arg	missense	Exon 1 of 1	NP_115706.1	Q96L46
	LPCAT2	NM_017839.5	MANE Select	c.1216-7678A>G		intron	N/A	NP_060309.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPNS2	ENST00000457326.3	TSL:6 MANE Select	c.197A>G	p.His66Arg	missense	Exon 1 of 1	ENSP00000400882.2	Q96L46
	LPCAT2	ENST00000262134.10	TSL:1 MANE Select	c.1216-7678A>G		intron	N/A	ENSP00000262134.5	Q7L5N7-1
	LPCAT2	ENST00000566915.5	TSL:1	n.1298-7678A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248880 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461608 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727068

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44650

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000248 AC: 3

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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.32
Sift	Benign	0.062	T
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.10
MutPred		0.18		Gain of helix (P = 0.062)
MVP		0.88
MPC		0.61
ClinPred		0.62	D
GERP RS		4.7
PromoterAI		-0.00060	Neutral
Varity_R		0.11
gMVP		0.31
Mutation Taster		=97/3	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: rs749172950; hg19: chr16-55600865;