NM_032646.6:c.1524+1268G>C

Variant names:

• chr17-74255101-G-C
• rs8078051
• NM_032646.6:c.1524+1268G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032646.6(TTYH2):​c.1524+1268G>C 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: 33)
• Consequence: TTYH2 NM_032646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 7 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032646.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTYH2	NM_032646.6	MANE Select	c.1524+1268G>C		intron	N/A	NP_116035.5
	TTYH2	NM_001330453.2		c.1461+1268G>C		intron	N/A	NP_001317382.1
	TTYH2	NM_052869.1		c.561+1268G>C		intron	N/A	NP_443101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTYH2	ENST00000269346.9	TSL:1 MANE Select	c.1524+1268G>C		intron	N/A	ENSP00000269346.4
	TTYH2	ENST00000441391.6	TSL:1	c.561+1268G>C		intron	N/A	ENSP00000394576.2
	TTYH2	ENST00000529107.5	TSL:2	c.1461+1268G>C		intron	N/A	ENSP00000433089.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.31

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

Other links and lift over

dbSNP: rs8078051; hg19: chr17-72251240;