ENST00000613192.2:n.-48T>C

Variant names:

• chr2-214809731-C-G
• ENST00000797167.1:n.176+86C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000613192.2(BARD1):​n.-162G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BARD1 ENST00000613192.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

Genes affected

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

BARD1 (HGNC:952): (BRCA1 associated RING domain 1) This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

BARD1 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613192.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BARD1	NM_000465.4	MANE Select	c.-162G>C		upstream_gene	N/A	NP_000456.2
	BARD1	NM_001282543.2		c.-162G>C		upstream_gene	N/A	NP_001269472.1
	BARD1	NM_001282545.2		c.-162G>C		upstream_gene	N/A	NP_001269474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG31	ENST00000797167.1		n.176+86C>G		intron	N/A
	BARD1	ENST00000260947.9	TSL:1 MANE Select	c.-162G>C		upstream_gene	N/A	ENSP00000260947.4
	BARD1	ENST00000617164.5	TSL:1	c.-162G>C		upstream_gene	N/A	ENSP00000480470.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 803830 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 405236

African (AFR) AF: 0.00 AC: 0 AN: 19490

American (AMR) AF: 0.00 AC: 0 AN: 26388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17246

East Asian (EAS) AF: 0.00 AC: 0 AN: 32186

South Asian (SAS) AF: 0.00 AC: 0 AN: 57650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 580154

Other (OTH) AF: 0.00 AC: 0 AN: 37838

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		-0.069
PromoterAI		0.12	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-215674455;