15-76950981-C-A

Position:

• chr15-76950981-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002902.3(RCN2):​c.*1759C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,276 control chromosomes in the GnomAD database, including 68,465 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 0.95 (68463 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: RCN2 NM_002902.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

RCN2 (HGNC:9935): (reticulocalbin 2) The protein encoded by this gene is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. This gene maps to the same region as type 4 Bardet-Biedl syndrome, suggesting a possible causative role for this gene in the disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCN2	NM_002902.3	c.*1759C>A		3_prime_UTR_variant	7/7	ENST00000394885.8	NP_002893.1
RCN2	NM_001271837.2	c.*1759C>A		3_prime_UTR_variant	8/8		NP_001258766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCN2	ENST00000394885.8	c.*1759C>A		3_prime_UTR_variant	7/7	1	NM_002902.3	ENSP00000378349	P1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143967 AN: 152154 Hom.: 68416 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.946 AC: 144071 AN: 152272 Hom.: 68463 Cov.: 32 AF XY: 0.947 AC XY: 70519 AN XY: 74428

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.984

Gnomad4 OTH AF: 0.958

Alfa AF: 0.958 Hom.: 10207

Bravo AF: 0.940

Asia WGS AF: 0.989 AC: 3441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.28

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: rs925492; hg19: chr15-77243322;