rs2697679

Variant names:

• chr8-89937652-A-C
• rs2697679
• NM_002485.5:c.2185-577T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-89937652-A-C
• chr8-89937652-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002485.5(NBN):​c.2185-577T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,034 control chromosomes in the GnomAD database, including 19,305 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 0.47 (19305 hom., cov: 32)
• Consequence: NBN NM_002485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 22 publications found

Genes affected

NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

NBN Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Orphanet, ClinGen
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• idiopathic aplastic anemia

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002485.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBN	NM_002485.5	MANE Select	c.2185-577T>G		intron	N/A	NP_002476.2
	NBN	NM_001024688.3		c.1939-577T>G		intron	N/A	NP_001019859.1	A0A0C4DG07
	NBN	NM_001440379.1		c.1939-577T>G		intron	N/A	NP_001427308.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBN	ENST00000265433.8	TSL:1 MANE Select	c.2185-577T>G		intron	N/A	ENSP00000265433.4	O60934
	NBN	ENST00000697309.1		c.2185-2040T>G		intron	N/A	ENSP00000513244.1	A0A8V8TKY5
	NBN	ENST00000697293.1		c.2236-577T>G		intron	N/A	ENSP00000513230.1	A0A8V8TM80

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72076 AN: 151916 Hom.: 19252 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72202 AN: 152034 Hom.: 19305 Cov.: 32 AF XY: 0.470 AC XY: 34930 AN XY: 74300

African (AFR) AF: 0.747 AC: 30954 AN: 41448

American (AMR) AF: 0.389 AC: 5949 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2436 AN: 5158

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4820

European-Finnish (FIN) AF: 0.315 AC: 3327 AN: 10556

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24863 AN: 67988

Other (OTH) AF: 0.452 AC: 953 AN: 2108

Alfa AF: 0.427 Hom.: 6243

Bravo AF: 0.487

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.4
DANN	Benign	0.76
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2697679; hg19: chr8-90949880; COSMIC: COSV55371358; COSMIC: COSV55371358;