rs8078051

Positions:

• chr17-74255101-G-A
• chr17-74255101-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032646.6(TTYH2):​c.1524+1268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,310 control chromosomes in the GnomAD database, including 416 homozygotes. 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: 𝑓 0.042 (416 hom., cov: 33)
• Consequence: TTYH2 NM_032646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

Genes affected

TTYH2 (HGNC:13877): (tweety family member 2) This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel, and may play a role in kidney tumorigenesis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH2	NM_032646.6	c.1524+1268G>A		intron_variant		ENST00000269346.9	NP_116035.5
TTYH2	NM_001330453.2	c.1461+1268G>A		intron_variant			NP_001317382.1
TTYH2	NM_052869.1	c.561+1268G>A		intron_variant			NP_443101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTYH2	ENST00000269346.9	c.1524+1268G>A		intron_variant		1	NM_032646.6	ENSP00000269346	P1
TTYH2	ENST00000441391.6	c.561+1268G>A		intron_variant		1		ENSP00000394576
TTYH2	ENST00000529107.5	c.1461+1268G>A		intron_variant		2		ENSP00000433089
TTYH2	ENST00000526858.1	c.*305+1268G>A		intron_variant, NMD_transcript_variant		5		ENSP00000462492

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6382 AN: 152192 Hom.: 409 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0421 AC: 6419 AN: 152310 Hom.: 416 Cov.: 33 AF XY: 0.0405 AC XY: 3013 AN XY: 74460

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.00978 Hom.: 9

Bravo AF: 0.0479

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.63

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: rs8078051; hg19: chr17-72251240;