20-62322431-C-T

Position:

• chr20-62322431-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005560.6(LAMA5):​c.6184G>A​(p.Asp2062Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,587,292 control chromosomes in the GnomAD database, including 264,392 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (19737 hom., cov: 34)
  • Exomes 𝑓: 0.58 (244655 hom.)
• Consequence: LAMA5 NM_005560.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5902873E-6).
• BP6: Variant 20-62322431-C-T is Benign according to our data. Variant chr20-62322431-C-T is described in ClinVar as [Benign]. Clinvar id is 1600279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA5	NM_005560.6	c.6184G>A	p.Asp2062Asn	missense_variant	47/80	ENST00000252999.7	NP_005551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7	c.6184G>A	p.Asp2062Asn	missense_variant	47/80	1	NM_005560.6	ENSP00000252999.3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71072 AN: 151880 Hom.: 19737 Cov.: 34

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.524

GnomAD3 exomes AF: 0.565 AC: 114690 AN: 203158 Hom.: 33791 AF XY: 0.573 AC XY: 63579 AN XY: 111038

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.546

Gnomad ASJ exome AF: 0.615

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.576

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.579 AC: 830496 AN: 1435294 Hom.: 244655 Cov.: 61 AF XY: 0.580 AC XY: 412759 AN XY: 711964

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.468 AC: 71074 AN: 151998 Hom.: 19737 Cov.: 34 AF XY: 0.472 AC XY: 35039 AN XY: 74292

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.529

Alfa AF: 0.535 Hom.: 11020

Bravo AF: 0.449

TwinsUK AF: 0.589 AC: 2185

ALSPAC AF: 0.583 AC: 2248

ESP6500AA AF: 0.151 AC: 647

ESP6500EA AF: 0.574 AC: 4883

ExAC AF: 0.535 AC: 62613

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.044
Sift	Benign	0.082	T
Sift4G	Benign	0.26	T
Polyphen		0.13	B
Vest4		0.11
ClinPred		0.0091	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2274934; hg19: chr20-60897487; COSMIC: COSV53361611; COSMIC: COSV53361611;