17-74244043-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032646.6(TTYH2):c.798G>A(p.Ala266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,611,288 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: TTYH2 NM_032646.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.22

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-74244043-G-A is Benign according to our data. Variant chr17-74244043-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.22 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTYH2	NM_032646.6	c.798G>A	p.Ala266=	synonymous_variant	6/14	ENST00000269346.9
TTYH2	NM_001330453.2	c.735G>A	p.Ala245=	synonymous_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTYH2	ENST00000269346.9	c.798G>A	p.Ala266=	synonymous_variant	6/14	1	NM_032646.6	P1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152196 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00118 AC: 294 AN: 248714 Hom.: 0 AF XY: 0.00114 AC XY: 153 AN XY: 134688

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000153

Gnomad NFE exome AF: 0.00211

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00170 AC: 2487 AN: 1458974 Hom.: 4 Cov.: 32 AF XY: 0.00170 AC XY: 1232 AN XY: 725872

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000138

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00154 AC: 234 AN: 152314 Hom.: 3 Cov.: 33 AF XY: 0.00145 AC XY: 108 AN XY: 74470

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00251

EpiControl AF: 0.00273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

TTYH2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.049
Dann	Benign	0.45

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: rs143670144; hg19: chr17-72240182;