chr2-210043987-C-T

Variant names:

• chr2-210043987-C-T
• NM_152519.4:c.1873G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152519.4(KANSL1L):​c.1873G>A​(p.Val625Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KANSL1L NM_152519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.954
• Publications: 0 publications found

Genes affected

KANSL1L (HGNC:26310): (KAT8 regulatory NSL complex subunit 1 like) Predicted to enable histone acetyltransferase binding activity. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL1L-AS1 (HGNC:41139): (KANSL1L antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11218271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152519.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1L	NM_152519.4	MANE Select	c.1873G>A	p.Val625Ile	missense	Exon 7 of 15	NP_689732.2
	KANSL1L	NM_001307976.2		c.1873G>A	p.Val625Ile	missense	Exon 7 of 14	NP_001294905.1	A0AUZ9-2
	KANSL1L-AS1	NR_110291.1		n.969+8743C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1L	ENST00000281772.14	TSL:5 MANE Select	c.1873G>A	p.Val625Ile	missense	Exon 7 of 15	ENSP00000281772.8	A0AUZ9-1
	KANSL1L	ENST00000418791.5	TSL:1	c.1873G>A	p.Val625Ile	missense	Exon 7 of 14	ENSP00000405724.1	A0AUZ9-2
	KANSL1L	ENST00000452086.5	TSL:1	c.1873G>A	p.Val625Ile	missense	Exon 7 of 8	ENSP00000401408.1	A0AUZ9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454134 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 723470

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000302 AC: 1 AN: 33102

American (AMR) AF: 0.00 AC: 0 AN: 43524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39044

South Asian (SAS) AF: 0.00 AC: 0 AN: 85246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108128

Other (OTH) AF: 0.00 AC: 0 AN: 60060

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T
Eigen	Benign	0.0037
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.95
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.038
Sift	Benign	0.18	T
Sift4G	Benign	0.42	T
Polyphen		0.43	B
Vest4		0.18
MutPred		0.14		Gain of helix (P = 0.2294)
MVP		0.072
MPC		0.058
ClinPred		0.49	T
GERP RS		4.4
Varity_R		0.057
gMVP		0.066
Mutation Taster		=94/6	polymorphism

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

hg19: chr2-210908711;