chr2-167135972-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_152381.6(XIRP2):c.472G>A(p.Glu158Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,611,940 control chromosomes in the GnomAD database, including 471 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.015 ( 34 hom., cov: 32)
Exomes 𝑓: 0.020 ( 437 hom. )
Consequence
XIRP2
NM_152381.6 missense
NM_152381.6 missense
Scores
1
14
Clinical Significance
Conservation
PhyloP100: 0.164
Genes affected
XIRP2 (HGNC:14303): (xin actin binding repeat containing 2) Enables actin filament binding activity. Predicted to be involved in actin cytoskeleton organization and heart development. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Colocalizes with focal adhesion and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.001642108).
BP6
?
Variant 2-167135972-G-A is Benign according to our data. Variant chr2-167135972-G-A is described in ClinVar as [Benign]. Clinvar id is 403612.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-167135972-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0154 (2344/152206) while in subpopulation SAS AF= 0.0491 (237/4826). AF 95% confidence interval is 0.044. There are 34 homozygotes in gnomad4. There are 1109 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XIRP2 | NM_152381.6 | c.472G>A | p.Glu158Lys | missense_variant | 3/11 | ENST00000409195.6 | |
XIRP2-AS1 | NR_046665.1 | n.154+4830C>T | intron_variant, non_coding_transcript_variant | ||||
XIRP2 | NM_001199143.2 | c.472G>A | p.Glu158Lys | missense_variant | 3/11 | ||
XIRP2 | NM_001079810.4 | c.472G>A | p.Glu158Lys | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XIRP2 | ENST00000409195.6 | c.472G>A | p.Glu158Lys | missense_variant | 3/11 | 5 | NM_152381.6 | ||
XIRP2-AS1 | ENST00000525330.1 | n.154+4830C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0154 AC: 2346AN: 152088Hom.: 33 Cov.: 32
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GnomAD3 exomes AF: 0.0189 AC: 4687AN: 247404Hom.: 80 AF XY: 0.0214 AC XY: 2879AN XY: 134296
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GnomAD4 exome AF: 0.0202 AC: 29534AN: 1459734Hom.: 437 Cov.: 30 AF XY: 0.0215 AC XY: 15646AN XY: 726176
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GnomAD4 genome ? AF: 0.0154 AC: 2344AN: 152206Hom.: 34 Cov.: 32 AF XY: 0.0149 AC XY: 1109AN XY: 74404
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ESP6500AA
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ESP6500EA
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;.
Polyphen
B;B;.
Vest4
MPC
0.023
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at