chr6-41335854-T-G

Position:

• chr6-41335854-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004828.4(NCR2):​c.-23T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,559,880 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00037 (3 hom.)
• Consequence: NCR2 NM_004828.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR2	NM_004828.4	c.-23T>G		5_prime_UTR_variant	1/5	ENST00000373089.10	NP_004819.2
NCR2	XM_017011500.2	c.2T>G	p.Met1?	start_lost	1/5		XP_016866989.1
NCR2	NM_001199509.2	c.-23T>G		5_prime_UTR_variant	1/6		NP_001186438.1
NCR2	NM_001199510.2	c.-23T>G		5_prime_UTR_variant	1/6		NP_001186439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR2	ENST00000373089	c.-23T>G		5_prime_UTR_variant	1/5	1	NM_004828.4	ENSP00000362181.5
NCR2	ENST00000373086	c.-23T>G		5_prime_UTR_variant	1/6	1		ENSP00000362178.3
NCR2	ENST00000373083	c.-23T>G		5_prime_UTR_variant	1/6	1		ENSP00000362175.4

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 631 AN: 151900 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.0000736

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000993 AC: 169 AN: 170162 Hom.: 0 AF XY: 0.000624 AC XY: 56 AN XY: 89700

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000580

Gnomad OTH exome AF: 0.000213

GnomAD4 exome AF: 0.000373 AC: 525 AN: 1407862 Hom.: 3 Cov.: 42 AF XY: 0.000322 AC XY: 224 AN XY: 695038

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.000659

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000923

Gnomad4 OTH exome AF: 0.000548

GnomAD4 genome AF: 0.00414 AC: 630 AN: 152018 Hom.: 5 Cov.: 31 AF XY: 0.00393 AC XY: 292 AN XY: 74286

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.0000403 Hom.: 32996

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.39

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: rs9394782; hg19: chr6-41303592;