rs971589098

Variant names:

• chr2-58159250-T-C
• rs971589098
• ENST00000449070.6:c.*515A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-58159250-T-C
• chr2-58159250-T-G

Variant summary

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

The NM_018062.4(FANCL):​c.*515A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000395 in 760,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: FANCL NM_018062.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• Publications: 0 publications found

Genes affected

FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]

VRK2 (HGNC:12719): (VRK serine/threonine kinase 2) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]

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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCL	NM_018062.4	c.*515A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000233741.9	NP_060532.2
VRK2	NM_006296.7	c.1183-99T>C		intron_variant	Intron 12 of 12	ENST00000340157.9	NP_006287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCL	ENST00000233741.9	c.*515A>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_018062.4	ENSP00000233741.5
VRK2	ENST00000340157.9	c.1183-99T>C		intron_variant	Intron 12 of 12	1	NM_006296.7	ENSP00000342381.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000395 AC: 3 AN: 760364 Hom.: 0 Cov.: 10 AF XY: 0.00000520 AC XY: 2 AN XY: 384764

African (AFR) AF: 0.00 AC: 0 AN: 18660

American (AMR) AF: 0.00 AC: 0 AN: 22400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15234

East Asian (EAS) AF: 0.00 AC: 0 AN: 35082

South Asian (SAS) AF: 0.00 AC: 0 AN: 41044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2540

European-Non Finnish (NFE) AF: 0.00000550 AC: 3 AN: 545066

Other (OTH) AF: 0.00 AC: 0 AN: 35548

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		0.61

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: rs971589098; hg19: chr2-58386385; COSMIC: COSV52078974; COSMIC: COSV52078974;