10-68406841-A-C

Position:

• chr10-68406841-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330103.2(RUFY2):​c.4+345T>G variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RUFY2 NM_001330103.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.202

Genes affected

RUFY2 (HGNC:19761): (RUN and FYVE domain containing 2) Enables SH3 domain binding activity. Predicted to be involved in regulation of endocytosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16679418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY2	NM_001330103.2	c.4+345T>G		intron_variant		ENST00000602465.6	NP_001317032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY2	ENST00000602465.6	c.4+345T>G		intron_variant		5	NM_001330103.2	ENSP00000473462	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4 AN: 1457826 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.22T>G (p.W8G) alteration is located in exon 1 (coding exon 1) of the RUFY2 gene. This alteration results from a T to G substitution at nucleotide position 22, causing the tryptophan (W) at amino acid position 8 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.92
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.72	N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.74	T
Polyphen		0.048	B
Vest4		0.58
MutPred		0.35		Loss of helix (P = 0.0093);
MVP		0.36
MPC		0.61
ClinPred		0.99	D
GERP RS		2.0
gMVP		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: rs769215045; hg19: chr10-70166598;