rs2402074

Positions:

• chr14-91827174-A-C
• chr14-91827174-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128596.3(TC2N):​c.-56-13349T>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TC2N NM_001128596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

Genes affected

TC2N (HGNC:19859): (tandem C2 domains, nuclear) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TC2N	NM_001128596.3	c.-56-13349T>G		intron_variant		ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3	c.-57+9197T>G		intron_variant			NP_001122067.2
TC2N	NM_001289134.2	c.-57+9197T>G		intron_variant			NP_001276063.2
TC2N	NM_152332.6	c.-57+9009T>G		intron_variant			NP_689545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7	c.-56-13349T>G		intron_variant		2	NM_001128596.3	ENSP00000387882	P1
TC2N	ENST00000340892.9	c.-57+9009T>G		intron_variant		1		ENSP00000343199	P1
TC2N	ENST00000360594.9	c.-57+9197T>G		intron_variant		1		ENSP00000353802	P1
TC2N	ENST00000556018.5	c.-57+9197T>G		intron_variant		2		ENSP00000451317

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.92

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: rs2402074; hg19: chr14-92293518;