2-210024194-T-G

Position:

• chr2-210024194-T-G

Variant summary

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

The NM_152519.4(KANSL1L):​c.2572A>C​(p.Ser858Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KANSL1L NM_152519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

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]

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=0.18917033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1L	NM_152519.4	c.2572A>C	p.Ser858Arg	missense_variant	14/15	ENST00000281772.14	NP_689732.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1L	ENST00000281772.14	c.2572A>C	p.Ser858Arg	missense_variant	14/15	5	NM_152519.4	ENSP00000281772.8
KANSL1L	ENST00000418791.5	c.2446A>C	p.Ser816Arg	missense_variant	13/14	1		ENSP00000405724.1
KANSL1L	ENST00000634716.1	n.*117A>C		non_coding_transcript_exon_variant	6/7	5		ENSP00000489299.1
KANSL1L	ENST00000634716.1	n.*117A>C		3_prime_UTR_variant	6/7	5		ENSP00000489299.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 26, 2024

The c.2572A>C (p.S858R) alteration is located in exon 14 (coding exon 13) of the KANSL1L gene. This alteration results from a A to C substitution at nucleotide position 2572, causing the serine (S) at amino acid position 858 to be replaced by an arginine (R). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0076	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.98	D;D
Vest4		0.24
MutPred		0.28		Gain of MoRF binding (P = 0.0286);.;
MVP		0.35
MPC		0.16
ClinPred		0.85	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs138434665; hg19: chr2-210888918;