2-210044061-A-T

Position:

• chr2-210044061-A-T

Variant summary

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

The NM_152519.4(KANSL1L):​c.1799T>A​(p.Met600Lys) variant causes a missense 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. 15/20 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)
• Consequence: KANSL1L NM_152519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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

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=0.12581518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1L	NM_152519.4	c.1799T>A	p.Met600Lys	missense_variant	7/15	ENST00000281772.14	NP_689732.2
KANSL1L-AS1	NR_110291.1	n.969+8817A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1L	ENST00000281772.14	c.1799T>A	p.Met600Lys	missense_variant	7/15	5	NM_152519.4	ENSP00000281772	P1
KANSL1L-AS1	ENST00000452057.1	n.1626+8817A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1799T>A (p.M600K) alteration is located in exon 7 (coding exon 6) of the KANSL1L gene. This alteration results from a T to A substitution at nucleotide position 1799, causing the methionine (M) at amino acid position 600 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.010	T;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.59	T;T;.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;L;L
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.29	T;T;T;T
Sift4G	Benign	0.31	T;T;D;D
Polyphen		0.43	B;B;B;B
Vest4		0.47
MutPred		0.39		Gain of disorder (P = 0.0182);Gain of disorder (P = 0.0182);Gain of disorder (P = 0.0182);Gain of disorder (P = 0.0182);
MVP		0.055
MPC		0.099
ClinPred		0.30	T
GERP RS		2.5
Varity_R		0.15
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-210908785;