rs1554427821

Variant names:

• chr7-150958265-G-A
• NM_000238.4:c.710C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-150958265-G-A
• chr7-150958265-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000238.4(KCNH2):​c.710C>T​(p.Pro237Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,294,272 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: KCNH2 NM_000238.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22213629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.710C>T	p.Pro237Leu	missense_variant	Exon 4 of 15	ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.710C>T	p.Pro237Leu	missense_variant	Exon 4 of 15	1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000532957.5	n.933C>T		non_coding_transcript_exon_variant	Exon 4 of 9	2
KCNH2	ENST00000684241.1	n.1543C>T		non_coding_transcript_exon_variant	Exon 2 of 13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1294272 Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1 AN XY: 637676

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: 9.66e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Uncertain	0.56	D;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	0.55	N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.7	D;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.048	D;T
Polyphen		0.018	B;.
Vest4		0.094
MutPred		0.20		Loss of glycosylation at P237 (P = 0.0223);.;
MVP		0.64
MPC		1.1
ClinPred		0.12	T
GERP RS		2.7
Varity_R		0.053
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr7-150655353;