1-36086294-A-G

Position:

• chr1-36086294-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014466.3(TEKT2):​c.488+253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,128 control chromosomes in the GnomAD database, including 64,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.92 (64700 hom., cov: 30)
• Consequence: TEKT2 NM_014466.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70

Genes affected

TEKT2 (HGNC:11725): (tektin 2) This gene product belongs to the tektin family of proteins. Tektins comprise a family of filament-forming proteins that are coassembled with tubulins to form ciliary and flagellar microtubules. This gene is expressed in the testis and its protein is localized to the flagella of the sperms, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-36086294-A-G is Benign according to our data. Variant chr1-36086294-A-G is described in ClinVar as [Benign]. Clinvar id is 1266573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.488+253A>G		intron_variant		ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.488+253A>G		intron_variant			XP_005270810.1
TEKT2	XM_011541258.4	c.488+253A>G		intron_variant			XP_011539560.1
TEKT2	XM_017001055.2	c.488+253A>G		intron_variant			XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.488+253A>G		intron_variant		1	NM_014466.3	ENSP00000207457	P1
TEKT2	ENST00000469024.1	c.*292+253A>G		intron_variant, NMD_transcript_variant		2		ENSP00000434183

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140092 AN: 152010 Hom.: 64643 Cov.: 30

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.922 AC: 140207 AN: 152128 Hom.: 64700 Cov.: 30 AF XY: 0.922 AC XY: 68536 AN XY: 74352

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.920

Alfa AF: 0.908 Hom.: 5291

Bravo AF: 0.924

Asia WGS AF: 0.968 AC: 3367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs408986; hg19: chr1-36551895;