6-41336093-A-G

Position:

• chr6-41336093-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004828.4(NCR2):​c.59A>G​(p.Gln20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,612,746 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (18 hom.)
• Consequence: NCR2 NM_004828.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188

Genes affected

NCR2 (HGNC:6732): (natural cytotoxicity triggering receptor 2) Predicted to enable signaling receptor activity. Predicted to be involved in cellular defense response and signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037223399).
• BP6: Variant 6-41336093-A-G is Benign according to our data. Variant chr6-41336093-A-G is described in ClinVar as [Benign]. Clinvar id is 714313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00748 (1139/152290) while in subpopulation AFR AF= 0.0244 (1014/41566). AF 95% confidence interval is 0.0231. There are 13 homozygotes in gnomad4. There are 537 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR2	NM_004828.4	c.59A>G	p.Gln20Arg	missense_variant	2/5	ENST00000373089.10	NP_004819.2
NCR2	NM_001199509.2	c.59A>G	p.Gln20Arg	missense_variant	2/6		NP_001186438.1
NCR2	NM_001199510.2	c.59A>G	p.Gln20Arg	missense_variant	2/6		NP_001186439.1
NCR2	XM_017011500.2	c.83A>G	p.Gln28Arg	missense_variant	2/5		XP_016866989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR2	ENST00000373089.10	c.59A>G	p.Gln20Arg	missense_variant	2/5	1	NM_004828.4	ENSP00000362181.5
NCR2	ENST00000373086.3	c.59A>G	p.Gln20Arg	missense_variant	2/6	1		ENSP00000362178.3
NCR2	ENST00000373083.8	c.59A>G	p.Gln20Arg	missense_variant	2/6	1		ENSP00000362175.4

Frequencies

GnomAD3 genomes AF: 0.00747 AC: 1137 AN: 152172 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00219 AC: 549 AN: 250306 Hom.: 12 AF XY: 0.00154 AC XY: 208 AN XY: 135212

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000295

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000345

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.00116 AC: 1695 AN: 1460456 Hom.: 18 Cov.: 34 AF XY: 0.00104 AC XY: 756 AN XY: 726316

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.000346

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.00748 AC: 1139 AN: 152290 Hom.: 13 Cov.: 32 AF XY: 0.00721 AC XY: 537 AN XY: 74464

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00176 Hom.: 3

Bravo AF: 0.00862

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0270 AC: 119

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00247 AC: 300

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.8
DANN	Benign	0.37
DEOGEN2	Benign	0.068	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.41	T;T;T
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.88	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.54	P;P;P
Vest4		0.086
MVP		0.48
MPC		0.15
ClinPred		0.0080	T
GERP RS		-0.89
Varity_R		0.027
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs34345974; hg19: chr6-41303831;