6-41350840-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_004828.4(NCR2):c.807T>C(p.Asp269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 885,666 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (18 hom.)
• Consequence: NCR2 NM_004828.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-41350840-T-C is Benign according to our data. Variant chr6-41350840-T-C is described in ClinVar as [Benign]. Clinvar id is 778229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00969 (1476/152328) while in subpopulation AFR AF= 0.0251 (1044/41582). AF 95% confidence interval is 0.0238. There are 18 homozygotes in gnomad4. There are 707 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR2	NM_004828.4	c.807T>C	p.Asp269=	synonymous_variant	5/5	ENST00000373089.10
NCR2	NM_001199509.2	c.*137T>C		3_prime_UTR_variant	6/6
NCR2	NM_001199510.2	c.*137T>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR2	ENST00000373089.10	c.807T>C	p.Asp269=	synonymous_variant	5/5	1	NM_004828.4	P2
NCR2	ENST00000373083.8	c.*137T>C		3_prime_UTR_variant	6/6	1		A2
NCR2	ENST00000373086.3	c.*137T>C		3_prime_UTR_variant	6/6	1		A2

Frequencies

GnomAD3 genomes AF: 0.00967 AC: 1472 AN: 152210 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00452 AC: 1043 AN: 230778 Hom.: 15 AF XY: 0.00411 AC XY: 513 AN XY: 124956

Gnomad AFR exome AF: 0.0262

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.0260

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000339

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00678

GnomAD4 exome AF: 0.00335 AC: 2458 AN: 733338 Hom.: 18 Cov.: 10 AF XY: 0.00310 AC XY: 1214 AN XY: 391970

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.00557

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000493

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00183

Gnomad4 OTH exome AF: 0.00810

GnomAD4 genome AF: 0.00969 AC: 1476 AN: 152328 Hom.: 18 Cov.: 33 AF XY: 0.00949 AC XY: 707 AN XY: 74476

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00560 Hom.: 4

Bravo AF: 0.0118

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

Invitae

Jun 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.46
Dann	Benign	0.42

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: rs115509322; hg19: chr6-41318578;