rs561562768

chr11-2445250-ACGCGCCCAT-Achr11-2445250-A-ACGCGCCCATchr11-2445250-A-ACGCGCCCATCGCGCCCAT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM4 BP6

The NM_000218.3(KCNQ1):c.160_168del(p.Ile54_Pro56del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000025 in 1,199,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: KCNQ1 NM_000218.3 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20

Genes affected

KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000218.3.
• BP6: Variant 11-2445250-ACGCGCCCAT-A is Benign according to our data. Variant chr11-2445250-ACGCGCCCAT-A is described in Lovd as [Benign]. Variant chr11-2445250-ACGCGCCCAT-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.160_168del	p.Ile54_Pro56del	inframe_deletion	1/16	ENST00000155840.12
KCNQ1	NM_001406836.1	c.160_168del	p.Ile54_Pro56del	inframe_deletion	1/15
KCNQ1	NM_001406838.1	c.160_168del	p.Ile54_Pro56del	inframe_deletion	1/11
KCNQ1	NM_001406837.1	c.-203_-195del		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.160_168del	p.Ile54_Pro56del	inframe_deletion	1/16	1	NM_000218.3	P1
KCNQ1	ENST00000646564.2	c.160_168del	p.Ile54_Pro56del	inframe_deletion	1/11
KCNQ1	ENST00000496887.7	c.24-125_24-117del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148266 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.51e-7 AC: 1 AN: 1051086 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 503790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000130

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148266 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000300

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397515877; hg19: chr11-2466480;