chr2-85611683-G-T

Position:

• chr2-85611683-G-T

Variant summary

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

The NM_001013649.4(C2orf68):​c.211C>A​(p.Leu71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,348 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C2orf68 NM_001013649.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39

Genes affected

C2orf68 (HGNC:34353): (chromosome 2 open reading frame 68)

USP39 (HGNC:20071): (ubiquitin specific peptidase 39) Predicted to enable thiol-dependent deubiquitinase and zinc ion binding activity. Involved in spliceosomal complex assembly. Located in nucleoplasm. Part of U4/U6 x U5 tri-snRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

C2orf68 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf68	NM_001013649.4	c.211C>A	p.Leu71Met	missense_variant	2/4	ENST00000306336.6	NP_001013671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf68	ENST00000306336.6	c.211C>A	p.Leu71Met	missense_variant	2/4	1	NM_001013649.4	ENSP00000304410.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418348 Hom.: 0 Cov.: 31 AF XY: 0.00000285 AC XY: 2 AN XY: 701906

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: 0.0000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Jun 18, 2021

The c.211C>A (p.L71M) alteration is located in exon 2 (coding exon 2) of the C2orf68 gene. This alteration results from a C to A substitution at nucleotide position 211, causing the leucine (L) at amino acid position 71 to be replaced by a methionine (M). 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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0076	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.19
Sift	Benign	0.23	T;T
Sift4G	Benign	0.091	T;T
Polyphen		1.0	D;D
Vest4		0.33
MutPred		0.40		Gain of MoRF binding (P = 0.0688);Gain of MoRF binding (P = 0.0688);
MVP		0.75
MPC		1.2
ClinPred		0.87	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.29
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-85838806;