2-149437773-C-T

Position:

• chr2-149437773-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194317.5(LYPD6):​c.65C>T​(p.Ala22Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYPD6 NM_194317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

Genes affected

LYPD6 (HGNC:28751): (LY6/PLAUR domain containing 6) Members of the LY6 protein family (see SLURP1; MIM 606119), such as LYPD6, have at least one 80-amino acid LU domain that contains 10 conserved cysteines with a defined disulfide-bonding pattern (Zhang et al., 2010 [PubMed 19653121]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28321576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYPD6	NM_194317.5	c.65C>T	p.Ala22Val	missense_variant	2/5	ENST00000334166.9	NP_919298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYPD6	ENST00000334166.9	c.65C>T	p.Ala22Val	missense_variant	2/5	1	NM_194317.5	ENSP00000334463.4

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

May 12, 2024

The c.65C>T (p.A22V) alteration is located in exon 2 (coding exon 1) of the LYPD6 gene. This alteration results from a C to T substitution at nucleotide position 65, causing the alanine (A) at amino acid position 22 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.98	N;N;D
REVEL	Benign	0.077
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.83	P;P;.
Vest4		0.27
MutPred		0.28		Gain of methylation at K21 (P = 0.082);Gain of methylation at K21 (P = 0.082);Gain of methylation at K21 (P = 0.082);
MVP		0.39
MPC		0.25
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.50

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: chr2-150294287;