7-150948437-G-T

Variant names:

• chr7-150948437-G-T
• NM_000238.4:c.2692+7C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000238.4(KCNH2):​c.2692+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: KCNH2 NM_000238.4 splice_region, intron
• Scores: Splicing: ADA: 0.0004497
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

Genes affected

KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.2692+7C>A		splice_region_variant, intron_variant	Intron 11 of 14	ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.2692+7C>A		splice_region_variant, intron_variant	Intron 11 of 14	1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000330883.9	c.1672+7C>A		splice_region_variant, intron_variant	Intron 7 of 10	1		ENSP00000328531.4
KCNH2	ENST00000684241.1	n.3525+7C>A		splice_region_variant, intron_variant	Intron 9 of 12

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000382 AC: 2 AN: 523180 Hom.: 0 Cov.: 16 AF XY: 0.00000726 AC XY: 2 AN XY: 275554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000265

Gnomad4 OTH exome AF: 0.0000456

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.014
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150645525;